# Integrated Review Plan for the National Ambient Air Quality Standards for Lead

External Review Draft[This page intentionally left blank.]EPA-452/D-11-001 March 2011



# Integrated Review Plan for the

National Ambient Air Quality Standards for Lead

External Review Draft

U. S. Environmental Protection Agency

National Center for Environmental Assessment Office of Research and Development and Office of Air Quality Planning and Standards Office of Air and Radiation

Research Triangle Park, North Carolina 27711March 2011 Draft – Do Not Quote or Cite 

### DISCLAIMER

This draft integrated review plan for the na tional ambient air quality standards for lead serves as a public information document and as a management tool for the U.S. Environmental Protection Agency's National Center for Envi ronmental Assessment and the Office of Air Quality Planning and Standards in conducting the review of the national ambient air quality standards for lead. The approach described in this draft plan may be modified for presentation in the final plan to reflect consultation with the Clean Air Scientific Advisory Committee and public comments. Subsequent modifications to th e plan may result from information developed during this review, and in consideration of a dvice and comments received from the Clean Air Scientific Advisory Committee and the public during the course of the revi ew. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.March 2011 i Draft – Do Not Quote or Cite 

### TABLE OF CONTENTS

1. INTRODUCTION ............................................................................................................... 1-1 1.1 LEGISLATIVE REQUIREMENTS ....................................................................... 1-1 1.2 OVERVIEW OF THE NAAQS REVIEW PROCESS ........................................... 1-3 1.3 REVIEW OF AIR QUALITY CRITERI A AND STANDARDS FOR LEAD ..... 1-8 1.4 SCOPE OF THE CU RRENT REVIEW................................................1-10

2. REVIEW SCHEDULE ........................................................................................................ 2-1

3. KEY POLICY-RELEVANT ISSUES ................................................................................. 3-1 3.1 ISSUES RELATED TO TH E PRIMARY NAAQS ............................................... 3-1 3.2 ISSUES RELATED TO TH E SECONDARY NAAQS ......................................... 3-2

4. SCIENCE ASSESSMENT .................................................................................................. 4-1 4.1 SCOPE AND ORGANIZATION ........................................................................... 4-1 4.2 ASSESSMENT APPROACH ................................................................................. 4-2 4.2.1 Introduction .............................................................................................. 4-2 4.2.2 Literature Search and Identific ation of Relevant Studies ........................ 4-4 4.2.3 Criteria for Study Selection ..................................................................... 4-4 4.2.4 Quality Assurance .................................................................................... 4-6 4.3 CONTENT AND ORGANIZATION OF THE ISA .............................................. 4-7 4.4 CAUSAL DETERMINATIONS .......................................................................... 4-15 4.5 SUPPLEMENTARY MATERIALS .................................................................... 4-15 4.6 SCIENTIFIC AND PUBLIC REVIEW ................................................................ 4-16 5. QUANTITATIVE RISK AND EX POSURE ASSESSMENT ............................................ 5-1 5.1 OVERVIEW OF ASSESSMENTS IN LAST REVIEW ........................................ 5-2 5.1.1 Human Exposure and Health Risk Assessments ..................................... 5-2 5.1.2 Ecological Risk Assessment .................................................................... 5-5 5.2 CONSIDERATION OF QUANTITATIVE ASSESSMENTS FOR THIS REVIEW ....................................................................................................... 5-7 5.2.1 Human Exposure and Health Risk Assessment ....................................... 5-7 5.2.2 Ecological Risk Assessment .................................................................. 5-11 5.3 SCIENTIFIC AND PUBLIC REVIEW .................................................................. 5-12

6. AMBIENT AIR MONITORING ......................................................................................... 6-1 6.1 Consideration of Samp ling and Analysis Methods .................................................... 6-1 6.2 Consideration of Air M onitoring Network Requirements ......................................... 6-2

7. POLICY ASSESSMENT AND RULEMAKING ............................................................... 7-1 7.1 Policy Assessment .................................................................................................... 7-1 7.2 Rulemaking ............................................................................................................ .... 7-3

8. REFERENCES ................................................................................................................. ... 8-1

APPENDIX A. INTEGRATED SCIENCE ASSESSMENT FOR LEAD – OUTLINE ............. A-1March 2011 1-1 Draft – Do Not Quote or Cite 

## 1 INTRODUCTION 1

The U.S. Environmental Protection Agency (EPA) is conducting a review of the air 2 quality criteria and the national ambient air qua lity standards (NAAQS) for lead (Pb). The 3 purpose of this document is to communicate the plan for this review. This review will provide 4 an integrative assessment of relevant scientific information for Pb and will focus on the basic 5 elements of the NAAQS for Pb: the indicator, 1 averaging time, form, 2 and level. These 6 elements, which together serve to define each ambient air quality standard, must be considered 7 collectively in evaluatin g the protection to public health and public welfare afforded by the 8
standards. 9 This draft Integrated Review Plan (IRP) cont ains the plans for this review of the air 10 quality criteria for Pb-related e ffects on public health and public welfare and of the current Pb 11 NAAQS. This draft IRP is being released for the purpose of consulting with the Clean Air 12 Scientific Advisory Committee (CASAC) and obtaining public co mment on the Agency’s plans. 13 The final IRP will be informed by comments received from the CASAC and the public. 14 This document is organized into eight chapters. Chapter 1 presents background 15 information on the review process, the legisla tive requirements for the review of the NAAQS, 16 and past reviews of the NAAQS for Pb. Chapte r 2 presents the current review schedule. 17 Chapter 3 presents a set of policy-relevant questi ons that will serve to focus this review on the 18
critical scientific a nd policy issues. Chapters 4 thr ough 7 discuss the planned scope and 19 organization of key assessment documents, the pl anned approaches for preparing the documents, 20 specific monitoring considerations and plans for sc ientific and public revi ew of the documents. 21 Complete reference citations are provided in chapter 8. 22



### 1.1 LEGISLATIVE REQUIREMENTS 23 Two sections of the Clean Air Act (CAA) gove rn the establishment and revision of the 24 NAAQS. Section 108 (42 U.S.C. section 7408) di rects the Administrator to identify and list 25 certain air pollutants and then to issue air quality criteria for those polluta nts. The Administrator 26 is to list those air pollutants th at in her “judgment, cause or cont ribute to air pollution which may 27 reasonably be anticipated to endanger public health or welfare;” “the presence of which in the 28
ambient air results from numerous or diverse mob ile or stationary sources;” and “for which . . . 29

1 The “indicator” of a standard defines the chemical species or mixture that is to be measured in determining whether an area attains the standard.

2 The “form” of a standard defines the air quality statistic that is to be compared to the level of the standard in determining whether an area attains the standard. For example, the form of the annual PM 2.5 NAAQS is the 3- year average of the we ighted annual mean PM 2.5 concentrations, while the form of the current 3-month Pb NAAQS is a 3-month average concentration not to be exceeded during a 3-year period.March 2011 1-2 Draft – Do Not Quote or Cite [the Administrator] plans to i ssue air quality criteria...” Air quality criteria are intended to 1 “accurately reflect the latest scie ntific knowledge useful in indicat ing the kind and extent of all 2 identifiable effects on public hea lth or welfare which may be e xpected from the presence of [a] 3 pollutant in the ambient air . . .” 42 U.S.C. § 7408(b). Section 109 (42 U.S.C. 7409) directs the 4 Administrator to propose and promulgate “pri mary” and “secondary” NAAQS for pollutants for 5 which air quality criteria are issued. Section 109 (b)(1) defines a primary standard as one “the 6 attainment and maintenance of which in the j udgment of the Administrator, based on such 7 criteria and allowing an adequate margin of sa fety, are requisite to protect the public health.” 3 A 8 secondary standard, as defined in section 109(b)(2), must “specify a level of air quality the 9 attainment and maintenance of which, in the ju dgment of the Administ rator, based on such 10 criteria, is requisite to protect the public welfare from any know n or anticipated adverse effects 11 associated with the presence of [the] pollutant in the ambient air.” 4 12 The requirement that primary standards provi de an adequate margin of safety was 13
intended to address uncertainties associated with inconclusive scientific and technical 14
information available at the time of standard set ting. It was also intende d to provide a reasonable 15 degree of protection against hazards that research has not yet identified. See Lead Industries 16
Association v. EPA , 647 F.2d 1130, 1154 (D.C. Cir 1980), cert. denied , 449 U.S. 1042 (1980); 17
American Petroleum Institute v. Costle , 665 F.2d 1176, 1186 (D.C. Cir. 1981), cert. denied , 455 18 U.S. 1034 (1982); American Farm Bureau Federation v. EPA, 559 F. 3d 512, 533 (D.C. Cir. 19 2009); Association of Battery Recyclers v. EPA , 604 F. 3d 613, 617-18 (D.C. Cir. 2010). Both 20 kinds of uncertainties are components of the risk associated with pollution at levels below those 21
at which human health effects can be said to occur with reasonable scientific certainty. Thus, in 22 selecting primary standards that provide an adeq uate margin of safety, the Administrator is 23 seeking not only to prevent pollution levels that ha ve been demonstrated to be harmful but also 24 to prevent lower pollutant levels that may pose an unacceptable risk of harm, even if the risk is 25 not precisely identified as to nature or degree. The CAA does not require the Administrator to 26 establish a primary NAAQS at a zero-risk leve l or at background concentration levels, see Lead 27
Industries v. EPA , 647 F.2d at 1156 n.51, but rather at a level that reduces risk sufficiently so as 28 to protect public health with an adequate margin of safety. 29

3 The legislative history of section 109 indicates that a primary standard is to be set at “the maximum permissible ambient air level . . . which will protect the health of any [sensitive] group of the population,” and that for this purpose “reference should be made to a repres entative sample of persons comprising the sensitive group rather than to a single person in such a group” S. Rep. No. 91-1196, 91st Cong., 2d Sess. 10 (1970).

4 Welfare effects as defined in section 302(h) (42 U.S.C. § 7602(h)) include, but are not limited to, “effects on soils, water, crops, vegetation, man-made materials, anim als, wildlife, weather, visibility and climate, damage to and deterioration of property, and hazards to transportation, as well as ef fects on economic values and on personal comfort and well-being.”March 2011 1-3 Draft – Do Not Quote or Cite In addressing the requirement for an adequate margin of safety, the EPA considers such 1 factors as the nature and severity of the health effects involved, th e size of sensitive population(s) 2 at risk, and the kind and degree of the uncertainties that must be addressed. The selection of any 3 particular approach to providing an adequate margin of safety is a policy choice left specifically 4 to the Administrator’s judgment. See Lead Industries Association v. EPA , 647 F.2d at 1161-62; 5 Whitman v. American Trucking Associations , 531 U.S. 457, 495 (2001). 6 In setting primary and secondary standards that are “requisite” to protect public health 7 and welfare, respectively, as provi ded in section 109(b), EPA’s task is to establish standards that 8 are neither more nor less stringent than necessary for these pur poses. In so doing, EPA may not 9 consider the costs of implementi ng the standards. See generally, Whitman v. American Trucking 10
Associations , 531 U.S. 457, 465-472, 475-76 (2001). Likewise, “[a]ttainability and 11 technological feasibility are not relevant considerations in the promulgation of national ambient 12 air quality standards.” American Petroleum Institute v. Costle , 665 F. 2d at 1185. 13 Section 109(d)(1) requires that “not later than Decemb er 31, 1980, and at 5-year 14 intervals thereafter, the Admini strator shall complete a thor ough review of the criteria 15 published under section 108 and the national ambient air quality st andards . . . and shall make 16
such revisions in such criteri a and standards and promulgate such new standards as may be 17 appropriate . . . .” Section 109(d)(2) requires th at an independent scie ntific review committee 18 “shall complete a review of th e criteria . . . and the national primary and secondary ambient air 19 quality standards . . . and sha ll recommend to the Administrato r any new . . . standards and 20 revisions of existing criteria and standards as ma y be appropriate . . . .” Since the early 1980's, 21 this independent review function has been pe rformed by the Clean Air Scientific Advisory 22 Committee (CASAC). 5 23



### 1.2 OVERVIEW OF THE NAAQS REVIEW PROCESS 24 Since completion of the last Pb NAAQS re view, the Agency has made a number of 25 changes to the process for reviewing the NAAQS. The current process, whic h is being applied to 26 this review of the NAAQS for Pb, has four majo r phases: (1) planning, (2) science assessment, 27 (3) risk/exposure assessment, and (4) policy assessment and rulemaking. An overview of the 28 process is illustrated in Figure 1-1 below and eachof these phases is described in this section. 6 29 The Agency maintains a web site on which ke y documents developed for NAAQS reviews are 30 made available ( http://www.epa.gov/ttn/naaqs/ ). 31

5 Lists of CASAC members and of members of the CASAC Pb Review Pa nel are available at: http://yosemite.epa.gov/sab/sabproduct.nsf/WebCASAC/CommitteesandMembership?OpenDocument

.
6 Information on changes to the NAAQS review process since the last Pb NAAQS review is available at: http://www.epa.gov/ttn/naaqs/review.html

.March 2011 1-4 Draft – Do Not Quote or Cite The planning phase of the NAAQS review process begins with a science policy 1 workshop, which is intended to iden tify issues and questions to fr ame the review. Drawing from 2 the workshop discussions, a draft IRP is pr epared jointly by EPA’s National Center for 3 Environmental Assessment (NCEA), within the Office of Research a nd Development (ORD), 4 and EPA’s Office of Air Quality Planning and St andards (OAQPS), within the Office of Air and 5 Radiation (OAR). The draft IRP is made ava ilable for consultation w ith CASAC and for public 6 comment. The final IRP is prepared in consid eration of CASAC and public comments. This 7 document presents the current plan and specifies the schedule for the entire review, the process 8 for conducting the review, and the key policy-relevant science issues that w ill guide the review. 9 The second phase of the review , science assessment, involv es the preparation of an 10 Integrated Science Assessment (ISA) and supplem entary materials. The ISA, prepared by 11 NCEA, provides a concise review, synthesis, and evaluation of the most po licy-relevant science, 12 including key science judgments th at are important to the design and scope of exposure and risk 13 assessments, as well as other aspects of the NAAQS review. The ISA and its supplementary 14 materials provide a comprehensive assessment of th e current scientific literature pertaining to 15 known and anticipated effects on pub lic health and welfare associat ed with the presence of the 16 pollutant in the ambient air, emphasizing informati on that has become available since the last air 17 quality criteria review in order to reflect the current state of knowledge. As such, the ISA forms 18 the scientific foundation for each NAAQS review a nd is intended to provide information useful 19 in forming judgments about air quality indicator( s), form(s), averaging time(s) and level(s) for 20 the NAAQS. Hence, the ISA and its associated materials function in the current NAAQS review 21 process as the Air Quality Criteria Document (AQC D) did in the previous review process. The 22 current review process generally includes producti on of a first and second draft ISA, both of 23 which undergo CASAC and public review prior to co mpletion of the final ISA. Section 4 below 24 provides a more detailed description of the pl anned scope, organization and assessment approach 25 for the ISA and its supporting materials. 26 In the third phase, the risk/exposure assessment phase, OAQPS staff considers 27 information and conclusions presented in the ISA, with regard to support provided for the 28 development of quantitative assessm ents of the risks and/or exposur es for health and/or welfare 29 effects. As an initial step, staff prepares one or more planning docum en ts that consider the 30 extent to which newly availabl e scientific evidence and tool s/methodologies warrant the conduct 31 of quantitative risk and exposur e assessments. To the extent warranted, this document(s) 32 outlines a general plan, including scope and methods, for conducting the assessments. This 33 planning document(s) is generally prepared in conjunction with th e first draft ISA and presented 34 for consultation with CASAC and for public comment. As discussed in chapter 5 below, this 35 planning document for the current Pb NAAQS review will focus on consideration of the newly 36March 2011 1-5 Draft – Do Not Quote or Cite available data, methods and tools in light of areas of uncertainty in the assessments conducted for 1 the last review and of the potential for new or updated assessments to provide notably different 2 exposure and risk estimates with lower associat ed uncertainty. Comments received on the 3 planning document(s) are considered in the Agency’s decision as to whether to conduct such 4 assessments. When an assessment is performed, one or more drafts of each risk and exposure 5 assessment document (REA) undergoes CASAC and public review, with the initial draft REA(s) 6 generally being reviewed in conj unction with review of the second draft ISA, prior to completion 7 of final REA(s). The REA provide s concise presentations of met hods, key results, observations, 8 and related uncertainties. Chapter 5 discusses po ssible approaches being c onsidered with regard 9
to human health- and welfare-related assessments for this review. 10 The review process ends with a policy a ssessment and rulemaking phase. Under the 11 current NAAQS review process (Jackson, 2009), the EP A Administrator has reinstated the use of 12 a Policy Assessment (PA). The PA, like the previous OAQPS Staff Paper, is a document that 13 provides a transparent OAQPS staff analysis and st aff conclusions regardi ng the adequacy of the 14 current standards and potential alte rnatives that are appropriate to consider prior to the issuance 15 of proposed and final rules. The PA integrates and interprets the information from the ISA and 16 REA(s) to frame policy options for consideration by the Administrator. Such an evaluation of 17 policy implications is intended to help ‘‘bridge the gap’’ between the Agency’s scientific 18 assessments, presented in the ISA and REA(s) , and the judgments required of the EPA 19 Administrator in determining whether it is approp riate to retain or revi se the NAAQS. In so 20 doing, the PA is also intended to facilitate CA SAC’s advice to the Agency and recommendations 21 to the Administrator on the adequacy of the existing standards or revisions that may be 22 appropriate to consider, as provi ded for in the CAA. In evaluating the adequacy of the current 23 standards and, as appropriate, a range of alternative standards, the PA considers the available 24 scientific evidence and, as available, quantitative risk-based analyses, together with related 25
limitations and uncertainties. The PA focuses on the information that is most pertinent to 26 evaluating the basic elements of national ambien t air quality standards: indicator, averaging 27 time, form, and level. One or more drafts of a PA are released for CASAC review and public 28 comment prior to completion of the final PA. 29 Following issuance of the final PA and consid eration of conclusions presented therein, 30 the Agency develops and publishes a notice of proposed rulemaking that communicates the 31
Adm inistrator’s proposed decisi ons regarding the standards re view. A draft notice undergoes 32 interagency review involving other fe deral agencies prior to publication. 7 Materials upon which 33

7 Where implementation of the proposed decision would have an annual effect on the economy of $100 million or more, e.g., by necessitating the implementation of emissions controls, EPA develops and releases a draft regulatory impact analysis (RIA) concurrent with the no tice of proposed rulemaking. This activity is conductedMarch 2011 1-6 Draft – Do Not Quote or Cite this decision is based, including the documents described above, ar e made available to the public 1 in the regulatory docket for the review. A pub lic comment period, during which public hearings 2 are generally held, follows publication of th e notice of proposed rulemaking. Taking into 3 account comments received on the proposed rule, 8 the Agency develops a final rule which 4 undergoes interagency review prior to publication to complete the rulemaking process. Chapter 5 7 discusses the development of the PA a nd the rulemaking steps for this review. 6

under Executive Order 12866. The RIA is conducted completely independent of and, by statute, is not considered in decisions regarding the review of the NAAQS.

8 When issuing the final rulemaking, the Agency responds to all significant comments on the proposed rule.March 20111-7Draft – Do Not Quote or CiteFigure 1-1.Overview of the NAAQS Review Process.Workshopon sciencepolicyissuesEPA finaldecision onstandardsInteragencyreviewCASAC consultationandpublic commentPeer-reviewedscientific studiesAgency decisionmaking and draftfinal noticePublic hearingsand commentson proposalIntegrated ReviewPlan: timeline andkey policy-relevantissues and scientificquestionsIntegrated Science Assessment:concise evaluation and synthesis of mostpolicy-relevant studiesCASAC reviewandpubliccommentAgency decisionmaking and draftproposal noticeInteragencyreviewPolicy Assessment:staff analysis ofpolicy options basedon integration andinterpretation ofinformation in the ISAand REARisk/Exposure Assessment:concise quantitative assessmentfocused on key results,observations, and uncertaintiesEPAproposeddecision onstandardsMarch 2011 1-8 Draft – Do Not Quote or Cite 

### 1.3 REVIEW OF AIR QUALITY CR ITERIA AND STANDARDS FOR 1 

### LEAD 2 On October 5, 1978, EPA initially promulgated primary and secondary NAAQS for Pb 3 under section 109 of the Act (43 FR 46246). Both pr imary and secondary standards were set at a 4 level of 1.5 micrograms per cubic meter ( μ g/m 3 ), measured as Pb in total suspended particles 5 (Pb-TSP), not to be exceeded by the maximum arithmetic mean concentration averaged over a 6 calendar quarter. These standards were based on the 1977 Air Quality Criteria for Lead (USEPA, 7 1977). 8
The first review of the Pb standards was initiated in the mid-1980s. The scientific 9
assessment for that review is described in th e 1986 Air Quality Criteria for Lead (USEPA, 10 1986a), the associated Addendum (USEPA, 1986b) and the 1990 Supplement (USEPA, 1990a). 11 As part of the review, the Ag ency designed and performed human exposure and health risk 12 analyses (USEPA, 1989), the results of which were presented in a 1990 Staff Paper (USEPA, 13 1990b). Based on the scientific assessment and the human exposure and hea lth risk analyses, the 14 1990 Staff Paper presented recommendations for consideration by the Ad ministrator (USEPA, 15 1990b). After consideration of the documents de veloped during the review and the significantly 16 changed circumstances since Pb was listed in 1976, the Agency did not propose any revisions to 17 the 1978 Pb NAAQS. In a parallel effort, the Agency developed the broad, multi-program, 18 multimedia, integrated U.S. Strategy for Reduci ng Lead Exposure (USEPA, 1991). As part of 19 implementing this strategy, the Agency focused efforts primarily on regulatory and remedial 20 clean-up actions aimed at reducing Pb exposures from a variety of nonair sources judged to pose 21 more extensive public health ri sks to U.S. populations, as well as on actions to reduce Pb 22 emissions to air, such as bringing more ar eas into compliance with the existing Pb NAAQS 23 (USEPA, 1991). 24 The most recent review of the Pb air quali ty criteria and standards was initiated in 25 November, 2004 (69 FR 64926) and the Agency’s plans for preparation of the Air Quality 26 Criteria Document and conduct of the NAAQS re view were contained in two documents: Project 27 Work Plan for Revised Air Quality Criteria for Lead (USEPA, 2005); and Plan for Review of the 28 National Ambient Air Quality Standards for Lead (USEPA 2006a). 9 The schedule for 29 completion of this review was governed by a ju dicial order in Missouri Coalition for the 30 Environment v. EPA (No. 4:04CV00660 ERW, Sept. 14, 2005; and amended on April 29, 2008 31 and July 1, 2008,), which specified a schedule for the review of duration substantially shorter 32 than five years. 33

9 In the current review, these two documents have been combined into an integrated plan (this document).March 2011 1-9 Draft – Do Not Quote or Cite The scientific assessment for the review is described in the 2006 Air Quality Criteria for 1 Lead (USEPA, 2006b), multiple drafts of which received review by CASAC and the public. 2 EPA also conducted human exposure and health ri sk assessments and a pilot ecological risk 3 assessment for the review, after consultation with CASAC and receiving public comment on a 4 draft analysis plan (USEPA, 2006c). Drafts of these quantitative assessm ents were reviewed by 5 CASAC and the public. The pilo t ecological risk assessment was released in December 2006 6 (ICF, 2006) and the final health risk assessment report was released in November 2007 (USEPA, 7 2007a). The policy assessment based on both of th ese assessments, air quality analyses and key 8 evidence from the AQCD was presented in the Staff Paper (USEPA, 2007b), a draft of which 9 also received CASAC and public review. Th e final Staff Paper presented OAQPS staff’s 10 evaluation of the public health and welfare policy implications of the key studies and scientific 11
information contained in the Crit eria Document and presented a nd interpreted results from the 12 quantitative risk/exposure analyses conducted for this review. Based on this evaluation, the Staff 13 Paper presented OAQPS staff recommendations that the Administrator gi ve consideration to 14 substantially revising the primary and secondary st andards to a range of levels at or below 0.2 15 micrograms per cubic meter (μg/m 3 ). 16 Immediately subsequent to completion of the Staff Paper, EPA issued an advance notice 17 of proposed rulemaking (ANPR) that was signe d by the Administrator on December 5, 2007 (72 18 FR 71488). 10 CASAC provided advice and recommendations to the Administrator with regard to 19 the Pb NAAQS based on its review of the ANPR a nd the previously released final Staff Paper 20 and Risk Assessment Report. The proposed deci sion on revisions to the Pb NAAQS was signed 21 on May 1, 2008 and published in the Federal Register on May 20, 2008 (73 FR 29184). In 22 addition to public comments on the proposal r eceived during the public comment period, both 23 written and oral at two p ublic hearings, the CASAC Pb Panel provided advice and 24
recommendations to the Administ rator based on its review of th e proposal notice. The final 25
decision on revisions to the Pb NAAQS was signed on October 15, 2008 and published in the 26 Federal Register on November 12, 2008 (73 FR 66964). 27
The November 2008 notice described EPA’s re visions to the primary and secondary 28 NAAQS for Pb. In consideration of th e much-expanded health effects evidence on 29 neurocognitive effects of Pb in children, EPA subs tantially revised the primary standard from a 30 level of 1.5 micrograms per cubic meter (μg/m 3 ) to a level of 0.15 μg/m 3 . EPA’s decision on the 31 level for the standard was based on the weight of the scientific evidence and guided by an 32 evidence-based framework that integrates evidence for relationships between Pb in air and Pb in 33

10 The ANPR was one of the features of the revised NAAQ S review process that EPA instituted in 2006. In 2009 (Jackson, 2009), this component of the proces s was replaced by reinstatement of the OAQPS policy assessment (previously termed the Staff Paper).March 2011 1-10 Draft – Do Not Quote or Cite children’s blood and Pb in children’s bl ood and IQ loss. The level of 0.15 μ g/m3 was estimated 1 to protect against air Pb-related IQ loss in the most highly exposed childr en, those exposed at the 2
level of the standard. Results of the quantitative ri sk assessment were judged supportive of the 3
evidence-based framework estimates. The av eraging time was revised to a rolling 3-month 4 period with a maximum (not-to-be-exceeded) form, evaluated over a 3-year period. As 5 compared to the previous averaging time of cale ndar quarter, this revision was considered to be 6 more scientifically appropriate and more health protective. The rolling average gives equal 7 weight to all three-month periods, and the new calculation method gives equal weight to each 8 month within each three-month period. Furthe r, the rolling average yields 12 three-month 9 averages each year to be compared to the NAAQ S versus four averages in each year for the 10 block calendar quarters pertaining to the previous standard. The indicator of Pb in total 11 suspended particles (Pb-TSP) was retained, reflec ting the evidence that Pb particles of all sizes 12 pose health risks. The secondary standard was re vised to be identical in all respects to the 13 revised primary standards. 11 14 Revisions to the NAAQS were accompanie d by revisions to the data handling 15 procedures, the treatment of exceptional events and the ambient air monitoring and reporting 16 requirements, as well as emissions inventory repor ting requirements. 12 As described in chapter 6 17 below, one aspect of the new data handling requi rements is the allowance for the use of Pb-PM 10 18 monitoring for Pb NAAQS attainment purposes in certain limited circumstances at non-source19 oriented sites. Subsequent to the 2008 rulemaking, additional revisions were made to the 20 monitoring network requirements as described in chapter 6 below. 21



### 1.4 SCOPE OF THE CURRENT REVIEW 22 For the current review of the Pb standards, relevant scientific information will be 23 assessed with regard to human e xposures and health effects associated with exposure to ambient 24 air-related Pb. The review will also assess any re levant scientific information associated with 25 known or anticipated public welfar e effects that may be identifie d. Unlike the other pollutants 26 for which NAAQS are established, Pb is a multimedia pollutant. Lead emitted into ambient air 27 may subsequently occur in multiple environmenta l media, contributing to multiple pathways of 28 exposure for humans and ecological receptors . This multimedia distribution of and 29

11 The current NAAQS for Pb are specified at 40 CFR 50.16.

12 The current federal regulatory measurement methods for Pb are specified in 40 CFR 50, Appendix G and 40 CFR part 53. Consideration of ambient air measurements with regard to judging attainment of the standards is specified in 40 CFR 50, Appendix R. The Pb monitoring network requirements are specified in 40 CFR 58, Appendix D, section 4.5. Guidance on the approach for implementation of the new standards was described in the Federal Register notices for the proposed and final rules (73 FR 29184; 73 FR 66964).March 2011 1-11 Draft – Do Not Quote or Cite multipathway exposure to air-related Pb has a key role in the Agency’s co nsideration of the Pb 1 NAAQS. Some associated considerati ons include the following (73 FR 66971): 2

 Lead emitted into the air is predominantly in particulate form, which can be transported 3 long or short distances de pending on particle size. 4

 Once deposited out of the air, Pb can subseque ntly be resuspended in the ambient air and, 5 because of the persistence of Pb, Pb emissi ons contribute to media concentrations for 6 some years into the future. 7

 Exposure to Pb emitted into the ambient ai r (air-related Pb) can occur directly by 8 inhalation, or indirectly by ingestion of Pb-c ontaminated food, water or other materials 9 including dust and soil. 13 These exposures occur as Pb emitted into the ambient air is 10 distributed to other environmental media and can contribute to human exposures via 11 indoor and outdoor dusts, outdoor soil, food and drinking water, as well as inhalation of 12 air. 13

 Air-related exposure pathways are affected by changes to air quality, including changes 14 in concentrations of Pb in air and changes in atmospheric deposition of Pb. Further, 15 because of its persistence in the environment, Pb deposited from the air may contribute to 16 human and ecological exposures for years into the future. Thus, the roles of both air 17 concentration and air deposition in human expos ure pathways, and the persistence of Pb 18 once deposited, influence the dynamics of th e response of the various Pb exposure 19 pathways to changes in air quality. 20

21
The current review of the Pb standards builds on the substantial body of work done 22 during the course of the last review. In addition to a comprehensive Air Quality Criteria 23 Document, EPA staff designed and conducted a co mplex multimedia, multipathway health risk 24 assessment involving case studies represented diffe rent ambient air Pb exposure circumstances, 25
and an assessment of the available informa tion on ecological impacts of Pb, including the 26 consideration of potentially vulne rable ecosystems. These differe nt types of information were 27 evaluated in a Staff Paper and provided the basis for the notice of proposed rulemaking and for 28
the substantial revisions made to the Pb NA AQS. In light of the extensive and detailed 29 quantitative analysis of health risk s in the last review, as well as the substantial revisions made to 30 the standard and the period of time elapsed si nce then in which new data may have been 31 collected, the information newly available in the current review will be considered with regard to 32 the extent to which an update or expansion to th e last quantitative risk assessment is warranted. 33

13 In general, air-related pathways include those pathways where Pb passes through ambient air on its path from a source to human exposure or to an ecological receptor.March 2011 2-1 Draft – Do Not Quote or Cite 

## 2 REVIEW SCHEDULE 1

In April 2010, EPA’s National Center for Environmental Assessment in Research 2 Triangle Park, NC (NCEA-RTP) announced the initia tion of the current periodic review of the 3 air quality criteria for Pb and the Pb NAAQS and issued a call for information in the Federal 4 Register (75 FR 20843). Also, as an initial step in the NAAQS review process described in 5 Section 1.1 above, EPA invited a wide range of external and intern al EPA experts, representing a 6 variety of areas of expertise (e.g., epidemio logy, human and animal toxicology, statistics, 7 risk/exposure analysis, atmospheric science) to participate in a works hop to discuss the policy8 relevant science to inform development of th is plan. This workshop was held May 10-11, 2010 9 in Research Triangle Park, NC (75 FR 20843). Th is workshop provided an opportunity for the 10 participants to broadly discuss the key policy -relevant issues around which EPA would structure 11 the Pb NAAQS review and to discuss the most m eaningful new science th at would be available 12 to inform our understanding of th ese issues. Based in part on th e workshop discussions, EPA has 13 developed this draft integrated review plan outlining the sche dule, the process, and the key 14 policy-relevant science issues that will guide the evaluation of the air quality criteria for Pb and 15 the review of the primary and secondary Pb NAAQS. 16
Table 2-1 outlines the schedule under which th e Agency is currently conducting this 17 review. The scopes of the review and of the key documents to be prepared during the review are 18 discussed throughout the rest of this document. 19March 2011 2-2 Draft – Do Not Quote or Cite Table 2-1. Proposed Schedule for Review of Ambient Air Quality Criteria and NAAQS for Pb.

Stage of Review Major Milestone Draft Target Dates Integrated Plan Literature Search Ongoing Federal Register Call for Information April 2010 Workshop on science/policy issues May 2010 Draft Integrated Review Plan (IRP) March 2011
CASAC consultation on IRP May 5, 2011
Final IRP June 2011
Science Assessment First draft of ISA End April 2011 CASAC public meeting for review of first draft ISA July 20-21, 2011
Second draft of ISA December 2011 CASAC/public review of second draft ISA February/March 2012
Final ISA June 2012 Risk/Exposure Assessment Planning document June 2011 CASAC public meeting for consultation on planning document July 21, 2011

If warranted, First draft risk and/or exposure assessments (REA) January 2012

CASAC/public review of first draft REA February/March 2012 Second draft REA July 2012 CASAC/public review of second draft REA September/October 2012 Final REA January 2013 Policy Assessment/ Rulemaking First draft of policy assessment (PA) CASAC/public review of first draft PA Second draft of PA CASAC/public review of second draft PA Final PA Notice of proposed rulemaking August 2012 September 2012 February 2013 March 2013 June 2013 January 2014 Notice of final rulemaking November 2014
1 2March 2011 3-1 Draft – Do Not Quote or Cite 

## 3 KEY POLICY-RELEVANT ISSUES 1

For our purposes in considering the overarchi ng questions regarding the adequacy of the 2 current Pb NAAQS, we have identifie d key policy-relevant issues to be addressed in this review. 3 They are presented below as a seri es of policy-relevant questions th at will frame our approach to 4 considering whether the current primary and secondary NAAQS for Pb should be retained or 5 revised. The ISA, REAs (if conducted), and PA developed in this new review will provide the 6 basis for addressing these questions and will info rm the Agency’s judgment as to the adequacy 7 of the current primary and secondary standards for Pb, and decisions as to whether to retain or 8
revise these standards. 9



### 3.1 ISSUES RELATED TO THE PRIMARY NAAQS 10 The first step in reviewing the adequacy of the current primary NAAQS is to consider 11 whether the available body of scientific evidence, assessed in the ISA, and used as a basis for 12 any analyses that might be presented in an REA, supports or calls into question the scientific 13 conclusions reached in the last review regarding health effects related to exposure to ambient air14
related Pb. This evaluation of the available scie ntific evidence will focus on key policy-relevant 15 issues by addressing a series of questions including the following: 16

 To what extent has new information altered th e scientific support fo r the occurrence of 17 health effects associated with exposure to levels of Pb found in the ambient air? 18

 To what extent has new information altered conclusions from previ ous reviews regarding 19 the plausibility of adverse health effects caused by Pb exposure? 20

 To what extent does the evidence suggest that alternate dose indicators other than blood 21 Pb levels should be evaluated to characterize the biological effect? 22

 At what levels of Pb exposure do health effects of concern occur? 23

 To what extent has new information alte red scientific conclu sions regarding the 24 relationships between Pb in ambient air a nd Pb in children’s blood and between Pb in 25 children’s blood and reduced IQ? 26

 Has new information altered our understan ding of human subpopul ations that are 27 particularly sensitive to Pb exposures? Is there new or emerging evidence on health 28 effects beyond neurocognitive endpoints in ch ildren that suggest additional sensitive 29 subpopulations should be given incr eased focus in this review? 30

 To what extent is key scientific ev idence becoming available to improve our 31 understanding of the health effects associated with various time periods of Pb exposures, 32 including not only daily, but also chronic (months to years) e xposures? To what extent is 33 critical research becoming available that could improve our un derstanding of the 34 relationship between various health endpoint s and different lag pe riods (e.g., single day, 35 multi-day distributed lags)? 36March 2011 3-2 Draft – Do Not Quote or Cite  To what extent do any risk or exposure anal yses developed for the review suggest that 1 exposures of concern for Pb-related health eff ects are likely to occur with current ambient 2 levels of Pb or with levels that just meet the Pb standard? If es timates are developed, are 3 the estimated risks/exposures of sufficient ma gnitude such that the health effects might 4 reasonably be judged to be important from a public health perspective? What are the 5 important uncertainties associated with any risk/exposure estimates? 6

 To what extent have important uncertainties identified in th e last review been reduced 7 and/or have new uncertainties emerged? 8

 To what extent does newly available informati on reinforce or call into question any of the 9 basic elements of the current Pb standard? 10 If the evidence suggests that revision of the current standa rds might be appropriate, EPA 11 will evaluate how the standards might be revised. Specifically, we will evaluate how the 12
scientific information and assessments inform d ecisions regarding the basi c elements of the Pb 13 NAAQS: indicator, averaging time, level, and form. These elements will be considered 14 collectively in evaluating the health protecti on afforded by the current or any alternative 15 standards considered. Specific policy-relevant questions that will be addressed include: 16

 To what extent is there any new informa tion that would support consideration of a 17 different indicator for Pb? 18

 To what extent does the health effects evidence evaluated in the ISA, air quality analyses 19 and, if available, the REA, provide support fo r considering different exposure indices or 20 averaging times? 21

 To what extent do air quality analyses and other information provide support for 22 consideration of altern ative standard forms? 23

 What range of alternative sta ndard levels should be consid ered based on the scientific 24 evidence evaluated in the IS A, air quality analyses and, if available, REA? 25

 What are the important uncertainties and limitations in that evidence and assessments and 26 how might those uncertainties and limitations be taken into consideration in identifying 27 alternative standards for consideration? 28


### 3.2 ISSUES RELATED TO THE SECONDARY NAAQS 29 As with the review of the primary NAAQS, th e first step in review ing the adequacy of 30 the current secondary NAAQS is to consider wh ether the available body of scientific evidence, 31 assessed in the ISA, and used as a basis for any analyses that might be presented in an REA, 32 supports or calls into question th e scientific conclusi ons reached in the la st review regarding 33 welfare effects related to exposur e to ambient air-related Pb. Th is evaluation of the available 34 scientific evidence will focus on key policy-relevant issues by addressing a series of questions 35 for each category of Pb-related welfare effects iden tified in the ISA as being associated with the 36 presence of Pb in the ambient air, while taking into account multimedia, multipathway 37

exposures: 38March 2011 3-3 Draft – Do Not Quote or Cite  To what extent does the available informa tion demonstrate or suggest that Pb-related 1 effects are occurring at current ambient conditions or at levels that would meet the 2 current standard? 3

 To what extent does the available informa tion inform judgments as to whether any 4 observed or anticipated effects are adverse to public welfare? 5

 To what extent is the current secondary st andard likely to be effective in achieving 6 protection against any identified adverse effects? 7

 Are there new empirical data or modeling re sults that would enha nce our understanding 8 of the movement of lead in ecosystems, or improve our understanding of bioavailability 9 and mechanisms of exposure? 10

 What new information is available about the nature of lead effects on aquatic 11 ecosystems? What new evidence is there regarding critical loads for these systems? 12

 Does the newly available evidence alter th e scientific support for lead effects on 13 terrestrial or aquatic ecosystem s associated with the levels of Pb found in ambient air? 14

 Does the newly available evidence indicate di fferent exposure levels at which ecological 15 receptors are expected to experience effects? 16

 What new information, methods or tools are av ailable to inform or facilitate assessment 17 of the accumulation and movement of air-de posited Pb through terrestrial and aquatic 18 ecosystems over time? 19

 To what extent does newly available informati on reinforce or call into question any of the 20 basic elements of the current Pb standard? 21 To the extent that the evidence suggests th at revision of the cu rrent secondary Pb 22 NAAQS would be appropriate to co nsider, the staff then identifies ranges of standards (in terms 23 of exposure indices, averaging times, levels, and forms) that would reflec t a range of alternative 24 policy judgments as to the degree of protection th at is requisite to prot ect public welfare from 25 known or anticipated adverse effects. In so doing, the staff addresses the following questions 26 taking into account multimedi a, m ultipathway exposures: 27

 Does the available information provide s upport for considering different Pb exposure 28 indices? 29

 Does the available information provide support for considering different averaging times? 30

 What range of levels and forms of alternat ive standards is suppor ted by the information, 31 and what are the uncertainties and li mitations in that information? 32

 To what extent do specific levels and form s of alternative standards reduce adverse 33 impacts attributable to Pb, and what are th e uncertainties in the estimated reductions? 34March 2011 4-1 Draft – Do Not Quote or Cite 

## 4 SCIENCE ASSESSMENT 1



### 4.1 SCOPE AND ORGANIZATION 2

The science assessment for Pb w ill consist of the ISA as well as supplementary materials 3 (see Section 4.5) if additional doc umentation is required to support information contained within 4 the ISA. The ISA will critically evaluate and integrate the scie ntific information on the health 5 and welfare effects associated with exposure to P b. The ISA is not intend ed to provide a detailed 6 literature review; but rather, will draw from the existing body of evidence to synthesize the 7 current state of knowledge on the most relevant i ssues pertinent to the re view of the NAAQS for 8 Pb. The ISA provides an updated comprehensive asse ssment of the current sc ientific literature 9 pertaining to known and anticipated effects on public health and welfare associated with the 10 presence of Pb in the ambient air, thus revising the assessment available at the time of the last 11
review. 12 Discussions in the ISA will primarily focus on scientific evaluations that can inform the 13 key policy questions described in Chapter 3 of this document. Although emphasis is placed on 14
discussion of health and welfare effects inform ation, other scientific information is also 15 presented and evaluated in order to provide a better understandi ng of the sources of Pb to 16 ambient air, measurement and concentrations of Pb in ambient air, its subsequent fate and 17 transport in the environment, pathways of hu man and ecological exposure, and toxicokinetic 18 characteristics of Pb in the human body, as we ll as the characterizati on of population exposures 19
to Pb. 20
The ISA will build on the conclusions of the lastreview of the air quality criteria for Pb, 21 presented in the 2006 air quality criteria document (AQCD) (U.S. EPA, 2006), and focus on peer 22 reviewed literature published ther eafter and on any new interpretati ons of previous literature. 23 The 2006 AQCD (U.S. EPA, 2006) evaluated litera ture published through December 2005. The 24 ISA will begin with a discussion of major legal an d historical aspects of prior review documents 25 as well as key milestones and pro cedures for document preparation. In subsequent chapters, the 26 results of recent scientific studies will be integr ated with previous findi ngs. Important older 27 studies may be discussed in detail to reinforce ke y concepts and conclusion s and/or if they are 28 open to reinterpretation in light of newer data. Older studies also may be the primary focus in 29
some areas of the document where research effort s have subsided, and these older studies remain 30
the definitive works available in the literature. Emphasis will be placed on studies that examine 31
effects associated with Pb concentrations relevant to current population and ecosystem 32 exposures, and particularly those pertaining to Pb concentrations currently found in ambient air. 33
Other studies m ay be included if th ey contain unique data, such as a previously unreported effect 34March 2011 4-2 Draft – Do Not Quote or Cite or mechanism for an observed effect, or examin e multiple concentrations to elucidate exposure1 response relationships. 2



### 4.2 ASSESSMENT APPROACH 3



### 4.2.1 Introduction 4

The EPA’s National Center for Environmenta l Assessment in Research Triangle Park 5 (NCEA-RTP) is responsible for preparing the ISA for Pb. In each NAAQS review, development 6 of the science assessment begins with a “Call for Information” published in the Federal Register. 7
This notice announces EPA’s initiation of activities in the preparation of the ISA for the specific 8 NAAQS review and invites the public to assist through the submissi on of research studies in the 9 identified subject areas. This and subsequent key components of the process currently followed 10 for the development of an ISA (i.e., the standard protocol) are presented in Figure 4.1. How the 11 ISA fits into the larger NAAQS review process is briefly described in section 1.2, the Overview 12 of the NAAQS Review Process. Important aspect s of the development of the ISA are described 13 in the sections below, including the approach for searching the literature and identifying relevant 14 publications and specific policy-re levant questions intended to guide the assessment. These 15 responsibilities are undertaken by expert authors of the ISA chapters that include EPA staff with 16 extensive knowledge in their respective fields and extramural scientists solicited by EPA for 17 their expertise in specific fields. The process for scientific and public review of drafts of the ISA 18
is described in Section 4.6. 19March 2011 4-3 Draft – Do Not Quote or Cite 1
Figure 4-1. Standard steps in the development of Integrated Science Assessments (ISAs). 2

3March 2011 4-4 Draft – Do Not Quote or Cite 

### 4.2.2 Literature Search and Identi fication of Relevant Studies 1 The NCEA-RTP will use a systematic approach to identify relevant studies for inclusion 2 in the Pb assessment. The EPA has already published a Federal Register notice (75 FR 8934, 3 February 26, 2010) to announce the initiation of this review and request information from the 4 public. In addition to the call for information, publications will be identified through an ongoing 5 literature search process that includes extensive computer database mining on specific topics in a 6 variety of disciplines. Additional publications will be identified by EPA scientists by reviewing 7 previous EPA reports and reviewing reference lis ts from key publications; studies also will be 8
identified in the course of CASAC and public review. 9 From the lists of publications broadly compile d from the search methods described above, 10 EPA will identify relevant studies to be reviewed as part of the assessment. Epidemiologic 11 studies, animal toxicological studi es, and studies of ecological or welfare effects of Pb, including 12 those related to exposure-response relationshi ps, mode(s) of action (MOA), and susceptible 13 populations and lifestages will be identified. Additionally, air quality and emissions data, studies 14 on atmospheric chemistry, environmental fate and transport, as well as issues related to Pb 15 toxicokinetics and exposure will also be identified. The assessment will include research 16 published or accepted for publication since the 2006 air quality review and through 17 approximately one month prior to the release of th e second external review draft of the ISA (see 18 Table 2-1). Studies published after that date may also be assessed if they provide new 19 information that impacts one or more key scientif ic issues. Once identified, studies are reviewed 20 with regard to quality assurance criteria descri bed in section 4.2.3 below before including them 21
in the assessment document. 22 The combination of the approaches de scribed here is expected produce the 23 comprehensive collection of studies to be included in the assessment and from which the most 24 informative and policy relevant studies will be selected for particular focus. 25



### 4.2.3 Criteria for Study Selection 26 In general, in assessing the scientific quali ty and relevance of health and environmental 27 effects studies, the following quality assurance criteria are consider ed when selecting studies for 28
inclusion in the ISA. 29
1. Are the study populations, subjects, or animal models adequately selected and are they 30 sufficiently well defined to allow for meani ngful comparisons between study or exposure 31 groups? 32

2. Are the statistical analyses appropriate, pr operly performed, and properly interpreted? 33 Are likely covariates adequately controlled or taken into account in the study design and 34 statistical analysis? 35

3. Are the air quality data, exposure, or dose metrics of adequate quality? 36March 2011 4-5 Draft – Do Not Quote or Cite 4. Are the health or welfare effect meas urements meaningful and reliable? 1

Studies published since the last air quality cr iteria review will be emphasized in the ISA; 2 however, evidence from studies described in last assessment that are needed to characterize the 3 current state of the science as well as new interpretations of older evidence will also will be 4
included in the assessment. 5 Among the studies included in the ISA, EP A will give particular focus to those 6 containing information in the following areas: 7
1. new studies with adequate da ta at the low end of the exposure distribution (e.g. <10 8 μg/dL blood); 9

2. new studies that provide quantitative effect estimates fo r populations or lifestages and 10 concentrations of interest; 11

3. Pb exposure or effects in suscep tible populations and lifestages; 12

4. issues related to the pote ntial for confounding of study e ffects/responses by non-Pb 13 exposure-related factors or va riables, and to the modifica tion of Pb-related effects; 14

5. the timing (e.g., across/within specific lifesta ges) and duration of exposure associated 15 with specific responses; 16

6. concentration-response relationships for specific Pb-related effects; 17

7. the interpretation of Pb biomarkers in epidem iological studies; and/or air-to-blood Pb or 18 air-to-bone Pb re lationships; 19

8. studies that evaluate Pb as a component of a complex mixtures of pollutants. 20

In selecting epidemiologic studies for incl usion in the present assessment, EPA will 21 consider studies containing information on (1) recen t or cumulative exposure s relevant to current 22 population exposure levels of Pb; (2 ) health endpoints that repeat or extend findings from earlier 23
assessments as well as those not previously extensively researched ; (3) populations and lifestages 24 that are susceptible to Pb exposures; (4) issues relate d to potential confounding, and 25 modification of effects; and/or (5) important m ethodological issues (e.g., timing and duration of 26 exposure, concentration-response relationships, in terpretation of biomarkers in epidemiological 27 studies, and air-to-blood/bone relationships) related to Pb exposure effects. In selecting the most 28 informative and policy relevant epidemiologic studies on which to give particular focus in the Pb 29 ISA, emphasis will be placed on those most releva nt to standard setting in the United States. 30
Informative studies conducted in other countries will be discussed, as appropriate (e.g. studies 31 for which the mean blood Pb level in the populati on studied is comparable to the current mean 32 blood Pb level in the corresponding U.S. population). 33 In reviewing new studies in the ISA that have evaluated the re sponse of laboratory 34 animals to Pb exposure, we will review studies th at reveal the effects of Pb exposure within the 35March 2011 4-6 Draft – Do Not Quote or Cite previously identified target biological systems (e.g. neurological, cardiovascular, renal, immune). 1 Additionally, particular focus will be given to those studies that involve doses or body burdens 2 that approximate human doses or body burden cond itions relevant to current U.S. exposures. 3 Studies at higher exposure or doses that result in body burdens above what is found in the current 4 U.S. population will be discussed when the study can provide information relevant to potential 5 mechanisms of action, information on exposure-re sponse relationships, or otherwise improve our 6 understanding of susceptible populations and lifestages. 7 In reviewing informative studies of welfare effects, emphasis will be placed on recent 8 studies that: (1) evaluate the occu rrence of effects associated with Pb exposure at current ambient 9 levels, with a particular focus on ambient leve ls resulting from ambient air Pb, and/or (2) 10 investigate the effects of Pb on ecosystems at a ny scale. Studies conducte d in geographical areas 11
outside the U.S. will be included in the assessment if they contribute to the general knowledge of 12 the effects of Pb irrespective of species or locality. As in the selection of health-related scientific 13 studies, welfare-related studies will be selected that advance our unders tanding of mechanisms 14 by which Pb directly affects terrestrial and aquatic biota. These mechanisms, as they pertain to 15 Pb exposures of short or longer duration, will inform our understandi ng of indirect effects that Pb 16 may exert more broadly on ecosystem structure, function and servic es. Key studies identified for 17 welfare effects will be integrated into the discus sion to inform our interpretation of the ecological 18
literature and our characterization of uncertainties. 19 The criteria described here pr ovide generalized benchmarks to guide the inclusion in the 20 ISA of the highest quality and mostpolicy-relevant studies. Deta iled critical analysis of all 21
studies of the effects of Pb on h ealth and welfare, especially in relation to the above criteria, is 22 beyond the scope of this document. Since the last scientific review was completed within the 23 past five years, it is expected that a consider able portion of the curren t ISA may be devoted to 24 summarizing previously available evidence that contribu ted to the basis for the last rulemaking. 25



### 4.2.4 Quality Assurance 26 NCEA participates in the Agency-wide Quality Management System, which requires the 27 development of a Quality Management Plan (QMP). Implementation of the NCEA QMP 28 ensures that all data generated or used by NCEA scientists are “of the type and quality needed 29 and expected for their intended us e” and that all information di sseminated by NCEA adheres to a 30 high standard for quality including objectivity, utility and integrity. Quality assurance (QA) 31 measures detailed in the QMP will be implemente d beginning with the start of the current Pb 32 review, including the development of the Pb ISA. 33 The NCEA QA staff is responsible for th e review and approval of quality-related 34 documentation. NCEA scientists are responsible for the evaluation of all inputs to the ISA, 35March 2011 4-7 Draft – Do Not Quote or Cite including primary (new) and secondary (existing) data, to ensure their quality is appropriate for 1 their intended purpose. NCEA follows the Data Quality Objectives, which identify the most 2 appropriate inputs to the science assessment, a nd provides QA instruction for researchers citing 3 secondary information. The approaches utilized to search the literatur e and criteria for study 4 selection were detailed in the two preceding subsections. Generally, NCEA scientists rely on 5 scientific information found in peer-reviewed journal articles, books, and government reports. 6 Where information is integrated or reduced from multiple sources to create new figures, tables, 7 or summation, the data generated are considered to be new and subject to rigorous quality 8

assurance measures to en sure their accuracy. 9



### 4.3 CONTENT AND ORGANIZATION OF THE ISA 10 Generally, the organization of the Pb ISA w ill be similar to the organization of the 11 integrative synthesis chapter of the 2006 Pb AQCD (U.S. EPA, 2006) and recent assessments for 12 other criteria pollutants (e.g. Car bon Monoxide (U.S. EPA, 2010)). 13 The ISA for Pb will contain information relevant to considering whether it is appropriate 14
to retain or revise the current ambient air Pb st andards. Decisions on the specific content of the 15 ISA will be guided by the series of policy-relevant questions outlined in Chapter 3 in addition to 16 a set of policy-relevant questions more specifically related to scientific evidence that may 17 become newly available in the current review pr ocess. These policy-rele vant questions for the 18 ISA are related to two overarching issues. The fi rst issue is the extent to which new scientific 19 evidence has become available that alters or substantiates the scientific evidence presented and 20 evaluated in the last Pb NAAQS review. The se cond issue is whether uncertainties from the last 21 air quality criteria review have been addressed and/or wh ether new uncertainties have emerged. 22 The specific questions related to th e review of the scientific literature for Pb that stem from these 23 two issues were derived from the last Pb NAAQS review, as well as from discussions of the 24
scientific evidence th at occurred at the May 2010 Science Policy Workshop for the current 25 review (75 FR 20843). These specific questions , which will guide decisions on content for the 26 Pb ISA, are listed below by topic area. 27

Source to Exposure

Ambient Air Sources and Multimedia Environmental Distribution : The ISA will present and 28
evaluate current information related to sources of Pb to ambient air, ambient air concentrations 29 and size distributions of Pb measured as a compone nt of particulate matter. Note that gas phase 30 Pb data are not available in the EPA Air Qualit y System (AQS) for asse ssment of Pb in the 31 vicinity of gaseous Pb emissions where leaded gasoline is still used (e.g. airports, certain 32 automotive racing facilities). The available info rmation will be presented concerning sources of 33March 2011 4-8 Draft – Do Not Quote or Cite freshly and previously emitted Pb including resusp ension of previously deposited Pb. The ISA 1 will evaluate relevant information concerning the tr ansport and fate of Pb released into the air 2 directly and via other environmental media (e .g., soil, surface and ground water). The ISA will 3 discuss Pb fluxes into and distribution among di fferent media. Where av ailable, the ISA will 4
draw from information in the l iterature about the bioavailabilit y of Pb in different media to 5 organisms based on the organisms’ biochemical characteristics. 6
The assessment will also describe the distribut ion of air monitors in the federal regulatory 7 Pb monitoring network and consider new studies th at address the precision and accuracy of the 8 Federal Reference and Federal Equivalent Method s (FRM and FEM, respectively) for Pb. The 9
assessment will also consider information on th e design of other air monitoring networks in 10 which Pb measurements are taken, such as the Chemical Speciation Network (CSN), Interagency 11 Monitoring of Protected Visual Environments (IMPROVE), and National Air Toxics Trends 12 Stations (NATTS). Additionally, new information regarding Pb techniques for the analysis of 13 particulate matter samples will be discussed. In reviewing the currently available evidence, we 14 will consider the following specific questions: 15
1. What new evidence is available on pr imary and secondary sources of Pb? 16

2. What new information is available regardi ng the fate and transport of Pb in the 17 environment? What new data exists to characterize atmospheric deposition and 18 resuspension of Pb. 19

3. What new information is available regard ing monitoring Pb in the environment and 20 analyzing Pb species within particulate matter samples? 21

4. What data are available to ch aracterize airborne Pb concentr ations, spatial and temporal 22 variability of concentrations, size distributions of Pb in the environment as a function of 23 different sources of Pb, and covariation of Pb concentrations with other ambient air 24 pollutant concentrations? 25

Exposure : The ISA will compile and evaluate evidence developed since the last assessment that 26 helps characterize the variability and uncertain ty in the relationships between ambient Pb 27 concentrations and exposures to Pb of humans and ecosystems relevant to the primary and 28 secondary standards. A conceptual model of Pb exposure through various pathways, including 29 exposure to airborne Pb and Pb deposited onto so il, as well as that whic h contributes to indoor 30 dust and dietary exposures, will be discussed. EPA will also assess studies relevant to the 31
assessment of errors in measurement or estimat ion of human exposure to Pb as well as the 32 possibly differential exposures of some populati ons. The following questi ons will be considered 33 during review of the available evidence: 34
1. What new evidence is available on exposure to Pb through air-related pathways? Can air35 related pathways be disentangled from wate r- and soil-related path ways using available 36 data? 37March 2011 4-9 Draft – Do Not Quote or Cite 2. What new evidence is available regarding obs ervational studies of Pb exposure? How do 1 these studies inform the assessment of exposure to air-related pathways? 2

3. What new studies address susceptib ility to elevated Pb exposure? 3

Toxicokinetics, Biological Markers, and Models of Lead Burden in Humans 4

The ISA will evaluate the literatu re relating to the toxicokinetics 14 of Pb, including the 5 application of available models to evaluate the storage of Pb in the body, biological markers of 6 Pb that indicate exposure and body burden, and the quantification of Pb exposure or dose from 7 air-related exposure pathways (e .g. air-to-blood ratios). During the last review, uncertainties 8 were identified including the blood Pb-air Pb relationship in slope-f actor models, and the 9 interpretation of blood Pb and bone Pb concentra tions reported in epidemiologic studies. The 10 ISA will consider these key uncertainties and ev aluate the extent to which new scientific 11 evidence may inform our ability to characteri ze and/or reduce those un certainties during the 12 current review. In reviewing the currently av ailable evidence, we will consider the following 13 specific questions: 14
1. What new evidence is available on biological and other factors that could affect the 15 distribution and accumulation of Pb into bl ood and bone (e.g., age, nutrition, gender, 16 race)? 17

2. What new evidence is available on population and lifestage variability in Pb biokinetics? 18

3. What new developments are available in bi okinetic models that can be used for 19 estimating impacts of multimedia human lead exposures on internal body burden, 20 generally indicated by blood or bone Pb levels ? Is there new evidence to inform our 21 understanding of the response of blood Pb to changes in ambient air Pb and associated 22 exposure pathways? 23

4. What new evidence is available to characteri ze biomarkers of concurrent and cumulative 24 exposures? What are the related uncertainti es with interpreting biomarker data for 25 exposure assessment? 26

5. How and to what extent does previous or concurrent Pb exposure, including duration 27 (e.g., acute, subchronic, chronic) and pattern (e.g., continuous low, extreme peak) impact 28 blood Pb and bone Pb? 29

6. What new evidence is available on the relatio nship between air Pb and blood Pb levels 30 and uncertainties in that relationship? What new knowledge exists regarding the 31 characterization of changes in this relationship when accounting for the multiple 32 pathways of Pb exposure and body burden associ ated with Pb exposure? What does the 33 current evidence indicate regard ing variation in the relations hip with variation in blood 34 Pb levels or air Pb levels? 35

14 The phrase toxicokinetics refers generally to the quantitative aspects and timing of absorption, distribution, biotransformation and excretion of xenobiotic chemicals in the body.March 2011 4-10 Draft – Do Not Quote or Cite 7. To what extent does new scientific ev idence increase our un derstanding of the 1 contributions of Pb from different sources and exposure pathways to blood Pb levels or to 2 other indicators of Pb body burden (e.g., contri butions from various air-related pathways, 3 including diet and indoor dust pathways)? 4

Human Health Effects

The ISA will evaluate the scientific litera ture related to neurological, cardiovascular, 5 renal, immune, hematological and other health effects associated with exposures to Pb. Building 6 upon the last review, EPA will continue to review the available epidemio logic and toxicological 7 evidence related to these health effects and, to th e extent data are availa ble, additional endpoints 8 (e.g., mortality, developmental, carcinogenic/mutageni c, and cellular outcomes ). The results of 9 new studies will be integrated with the previous findings and with any new interpretations of 10 previous findings. The ISA will also integrate previous information on susceptible populations 11 and lifestages (e.g., children, lactating wome n, and older adults) or factors affecting 12 susceptibility (e.g., genetic polymorphisms and health status) with any new evidence on 13 susceptibility factors, li festages or populations. 14 For a given type of health outcome, the ISA will fully integrate findings across the 15 different disciplines to evalua te the strength, robustness and consistency of evidence, which 16
contribute to EPA’s assessment of causal relatio nships. Integration will also entail using the 17 toxicological findings to assess biological plausibility for th e epidemiologic findings, including 18 the coherence of epidemiologic obs ervations with known mechanisms of toxicity. Efforts will be 19 directed at identifying the lower blood Pb levels at which adverse effects are observed and at 20 describing concentration-response re lationships with a focus on Pb exposures at the lower end of 21 the distribution. Concentration-response relations hips also will be evaluated for comparability 22
across the studies. Another area of focus includes assessment of the durations of exposure and 23 specific developmental periods of exposure that are most strongly associated with particular 24
health effects. The ISA will also assess th e evidence for uncertainties related to these 25 associations and evaluate information on the public health implications related to ambient Pb 26 exposure. Grouped by topic area, some of the speci fic scientific questions that EPA will seek to 27
address in the ISA are as follows: 28

Health Endpoints: The ISA will evaluate health effects evidence for a multitude of outcomes 29 assessed in epidemiologic and toxicological st udies guided by the following questions: 30
1. How do results of recent epidemiologic stud ies and current or ne w interpretations of 31 previous findings expand our understanding of the relationship between body burdens 32 of Pb and neurological effects in children and adults, includi ng deficits in IQ, 33 behavior, learning, and motor skills, as we ll as risk of neurode generative diseases? 34 What new evidence is available on the potential clinical relevance of these effects? 35March 2011 4-11 Draft – Do Not Quote or Cite Do recent studies expand the current understanding of concentration-response 1 relationships pertinent to th e range of Pb exposures curre ntly experienced by the U.S. 2 population? 3

2. How do different indicators of Pb body bur dens (e.g., Pb in blood or bone) compare 4 in terms of their associati ons with adverse health outco mes? What do these findings 5 contribute to the understandi ng of how effects may differ for more recent and 6 cumulative lifetime exposure? 7

3. What new epidemiological evidence is ava ilable on health outcomes associated with 8 measures of Pb exposure in the elderl y (e.g., total mortalit y and cardiovascular 9 mortality)? What does such evidence indi cate regarding the pot ential for different 10 impacts of early-life, current, a nd cumulative lifetim e Pb exposures? 11

4. Within the epidemiologic literature, is there consistency between associations 12 observed in children and adults and be tween related health outcomes (e.g., 13 cardiovascular and renal)? 14

5. Does new evidence from the literature on effects observed in adult animals in 15 response to experimental exposures to Pb during development inform the 16 understanding of populations and life stages th at are susceptible to Pb exposure (e.g., 17 children, elderly, obese)? Within the sensitive in utero period of de velopment, is there 18 evidence of Pb causing epigenetic change s or evidence of Pb effects differing 19 between the sexes or genetic variants? 20

6. For what Pb-induced health effects, is ther e sufficient evidence in multiple species to 21 support a quantitative comparison of exposures that induce the effects? 22

7. To what extent does exposure to Pb contribut e to health effects in organ systems other 23 than the neurological, cardiovascular , and renal systems (e.g., hepatic, 24 gastrointestinal, skeletal)? Is there epidemiological ev idence that Pb exposure is 25 associated with new biological markers of effect (e.g. cortisol, brain imaging 26 endpoints, glomerular filtra tion) that combined with mechanistic evidence may 27 support conclusions regarding biological plausibility? 28

8. What new evidence has becom e available to help discern how the effects of Pb 29 exposure on a health outcome are modified when it occurs within mixtures that 30 include other toxic metals, ambient polluta nts, or other environmental exposures 31 versus Pb alone (e.g., additive, synergistic, or antagonistic effects)? 32

Uncertainties : The ISA will evaluate uncertainty in the sc ientific data, particularly in relation to 33 observed epidemiologic findings and their consiste ncy with toxicological studies in terms of 34 observed effects and biological pathways. In this vein, the following questions will be 35
considered: 36
1. To what extent are the health effects obser ved in epidemiological studies attributable 37 to exposure to Pb rather than co-exposures to other toxic metals or environmental 38 contaminants? 39

2. In epidemiologic studies, what are the uncertainties in Pb effect estimates due to 40 potential confounding factors (e.g., dem ographic and lifestyle attributes, 41March 2011 4-12 Draft – Do Not Quote or Cite socioeconomic status [SES], genetic suscep tibility factors, occupational exposure, 1 and access to medical care)? 2

3. Based on the new body of evidence, what uncer tainties remain regarding the nature 3 and shape of concentration -response relationships (e.g., th reshold, linear, nonlinear)? 4 What evidence is newly available on the unc ertainties related to other aspects of 5 statistical model specification and how can it be used to assess the influence of these 6 uncertainties on the results of epidemiologic studies? What evidence is available 7 from toxicological studies of dose-response relationships? 8

4. What uncertainties surround the evidence for long-term effects such as those that 9 shorten life duration and/or affect the development or progression of disease? 10

Biological Mechanism(s) or Modes of Action : In evaluating the current information from 11 studies that investigate mechanisms for the hea lth outcomes that have been associated with 12 exposure to Pb, EPA will address the following questions in the ISA: 13
1. To what extent is evidence now availabl e regarding mechanis ms for neurological 14 effects associated with “lower” (< 10 μg /dL or < 5 μg/dL) blood Pb levels (e.g., 15 oxidative stress)? What toxicological evid ence is available on mechanisms and dose16 response relationships for other health outcomes (e.g., cardiovascular, renal, or 17 immunological effects) or dose metrics, a nd is there coherenc e between this and 18 epidemiologic findings for these endpoints? 19

2. To what extent is key evidence now avai lable regarding mechanisms of action and 20 concentration-response relationships at various ages and developmental stages, 21 including critical windows of exposure that re sult in different effects and/or effects at 22 lower exposures? Are new animal models available to better characterize 23 mechanisms of action at various lifestages? 24

3. What mechanistic evidence is available on common modes of action that would help 25 our understanding of health effects of exposur e to Pb when it occurs within mixtures 26 versus alone (e.g., evidence for additive, synergistic, or anta gonistic effects)? 27

Susceptible Populations and Lifestages : The ISA will examine the evidence for different health 28 effects or outcomes to identify specific population groups that may have a greater likelihood of 29 experiencing health effects re lated to Pb exposure. In id entifying these groups, the ISA will 30 consider a variety of defining factors including, but not lim ited to lifestage (e.g., childhood), 31 lifestyle (e.g., smoking status, nutrition), genetic or developmental factors, race, sex, preexisting 32 disease, access to health care, and factors affecting exposur e to Pb such as neighborhood 33 characteristics. In the ISA, the evaluation of susceptibility factors will consider the following 34
issues: 35
1. To what extent is key new evidence availa ble that could inform the understanding of 36 populations that are particular ly susceptible to Pb expos ures? What is known about 37 genetic traits, pre-existing conditions (obesity), or other factors that affect susceptibility 38 (sex)? To what extent is the strength of ep idemiologic or toxicological evidence driven 39 by effects observed in populations with increased su sceptibility? 40March 2011 4-13 Draft – Do Not Quote or Cite a. Is there evidence from new animal models of susceptibility factors that improves 1 our characterization of susceptible popul ations and is there coherence between 2 findings for these models and epidemiologic findings? 3

2. To what extent is key evidence now avai lable to inform our understanding of 4 developmental lifestages that are particularly susceptible to Pb exposures? What is 5 known about critical windows of exposure fo r Pb with regard to their impact on 6 concentration-response relationshi ps and/or effects elicited? 7

a. To what extent is susceptibility to the e ffects of early life Pb exposure associated 8 with the development and or persistence/pr ogression of Pb eff ects in adults? Are 9 there new animal models that follow these windows of susceptibility? 10

b. Are new animal models available that ma y help us to characterize the critical 11 windows of exposure to Pb and, is there coherence between findings from these 12 models and epidemiologic findings? Do any of these models show differential 13 responses by sex of the animal? 14

3. What do the currently available studies i ndicate regarding the relationship between 15 exposures to Pb and health effects in those with preexisting diseases (e.g., renal diseases) 16 compared to healthy individuals? What me dical conditions are id entified as increasing 17 susceptibility to Pb effects? What is the nature and time-course of the development of 18 effects in previously healthy persons and in persons with pre-existing disease (e.g., 19 cardiovascular disease)? What are the pathways and mechanisms through which Pb may 20 be acting for these groups? 21

Public Health Implications: The ISA will present concepts th at integrate evidence on Pb-related 22 health effects and consequent publ ic health significance to assist in the assessment of the public 23 health implications of exposure to Pb in ambi ent air. Development of these concepts may 24
include consideration of estimates of the sizes of identified sus ceptible populations (e.g., adults 25 with cardiovascular disease, children) and discus sion of the public hea lth significance of the 26 magnitudes of change in health outcomes conclu ded to result from air-related Pb exposures. 27

Ecological and Other Welfare Effects 28

The ISA will evaluate the curren t literature related to effect s of Pb exposures in aquatic 29 and terrestrial ecosystems at all scales, as avai lable. Evidence relate d to any other welfare 30 effects (e.g. visibility, climate, ma terials) will be considered, if av ailable. Publications will be 31 evaluated for causal relationships between Pb at am bient levels and ecological effects. Studies at 32 higher than ambient Pb exposures will be evaluated to the extent they can inform the 33 interpretation of the effects of exposures that are currently widespread in the environment. In the 34 last review, EPA recognized the pe rsistence of Pb in the envir onment, and concluded that the 35 combination of Pb accumulated from past deposition, and much smaller ongoing deposition 36 continue to cause ecological eff ects in terrestrial and aquatic ecosystems (U.S. EPA, 2006). If 37 available, new studies pertaining to the recycling of Pb in aquatic and terrestrial ecosystems, and 38March 2011 4-14 Draft – Do Not Quote or Cite to the role of previously sequestered Pb in current ecosystem processes, including its 1 contribution to total loading, will be discussed. This discussion will in clude evaluation of the 2 effect of Pb on ecosystem productiv ity and of the potential effects of Pb on ecosystem services. 3
Sources of Pb that are not rele vant to consideration of air-related Pb (e.g. Pb shot) were not 4 considered. Some scientific questions that EP A will seek to address in the ISA follow, grouped 5 by topic area. 6

Terrestrial Ecosystem Effects : 7

1. What new information is available about the nature of the effects of Pb on terrestrial 8 ecosystems, especially Pb that is relevantto air-related pathways? Is there new 9 evidence of effects at current ecosystem lo ads? Is there new evidence that, in 10 combination with the previously existi ng evidence, supports the development of 11 critical loads for terrestrial ecosystems? 12

2. Is there new information available for establishing specific exposure levels at which 13 terrestrial ecological receptors are ex pected to experience effects? 14

3. Are there new empirical data or mode ling results that would improve our 15 understanding of the movement of Pb in or through terrestrial systems, or would 16 improve our understanding of Pb bioavail ability and pathways of exposure for 17 terrestrial organisms? 18

4. Is there new evidence that contributes to a be tter understanding of the nature and 19 magnitude of the potential effects of Pb on terrestrial ecosystem services? 20

Aquatic Ecosystem Effects : 21

1. What new information is available about th e nature of the effects of Pb on aquatic 22 ecosystems, especially Pb that is relevantto air-related pathways? Is there new 23 evidence of effects at current ecosystem lo ads? Is there new evidence that, in 24 combination with the previously existing ev idence, supports the de finition of critical 25 loads for aquatic ecosystems? 26

2. Is there new information available for establishing specific exposure levels at which 27 aquatic ecological receptors are expe cted to experience effects? 28

3. Are there new empirical data or mode ling results that would improve our 29 understanding of the movement of Pb in or through aquatic systems or would 30 improve our understanding of Pb bioavailabil ity and pathways of exposure for aquatic 31 organisms? 32

4. Is there new evidence that contributes to a be tter understanding of the nature and 33 magnitude of the potential effects of Pb on aquatic ecosystem services? 34

35March 2011 4-15 Draft – Do Not Quote or Cite 

### 4.4 CAUSAL DETERMINATIONS 1 In evaluating and integrating the different type s of evidence from recen t studies with that 2 available during the previous reviews, the ISA wi ll draw conclusions regarding the strength of 3 the evidence in describing causal relationships between relevant blood Pb, bone Pb or other 4 exposure metrics and health effects and relevant Pb concentrations and environmental effects. 5 Since the last Pb NAAQS review, EPA has develope d a framework that is intended to provide a 6 consistent and transparent basi s for drawing such conclusions. 15 Briefly, the framework includes 7 the following considerations for drawing conc lusions of causality for specific endpoints: 8 consistency of findings for an e ndpoint across studies in which it was examined, coherence of the 9 results related to a specific e ndpoint among different study types or disciplines, the coherence of 10
results with characterized mechan isms of action (biological plausibility), and evidence of a 11 concentration- or dose-response relationship for an endpoint. In the ISA, in considering the 12 strength of the evidence with regard to demonstr ating that exposure to ambient air-related Pb, in 13 particular, causes specific health effects, EPA will give particular attention to studies that 14 examine Pb exposures relevant to those currentl y occurring in the U.S. population or ecosystems. 15



### 4.5 SUPPLEMENTARY MATERIALS 16

Previous science assessments conducte d to support NAAQS reviews included 17 supplementary materials, which were designed to provide detailed suppo rting information and 18 more comprehensive coverage of the research areas summarized in the ISA. NCEA intends to 19 change the form, while maintaining the relevant content, of the materials that were formerly 20
contained within the Annexes to the ISA. 21 As discussed previously, studies included in the text of the ISA will be those deemed 22 informative to the NAAQS review process (e.g. po licy-relevant) and of adequate quality. The 23 ISA text, tables and figures will highlight and summarize key study details that are needed to 24 understand and interpret th e results of a study. This information, which was described in the text 25
as well as reiterated in the anne x tables of previous documents, includes the air quality system 26 (AQS) data; studies of fate and transport in ai r, water, and soil; human exposure and dosimetry 27 studies; blood Pb, bone Pb or ot her exposure metrics corresponding to adverse health effects and 28 dose and duration of exposure in toxicological st udies; and, effect esti mates, study location and 29 time period, population, exposure metric and time wi ndow, as well as the ch aracteristics of the 30 exposure/dose distribution for epidemiologic studie s. In addition, supplementary materials will 31 be provided in the form of output from the Heal th and Environmental Research Online (HERO) 32 database. A key function of the HERO output wi ll be to document the base of evidence 33

15 Use of this framework in the recent science assessment for particulate matter is described in chapter 1 of that ISA (EPA, 2009a).March 2011 4-16 Draft – Do Not Quote or Cite containing publications evaluated for the Pb re view, including any publi cations considered but 1 not included in the ISA. This information will be pr esented as links to lists of references in the 2 HERO database, which include bibliographic in formation and abstracts. In addition, certain 3 study characteristics of epidemiologic studies, including location, ages in vestigated, outcomes, 4 and health endpoints, will be summarized in ta bles developed from HE RO extracted study data. 5



### 4.6 SCIENTIFIC AND PUBLIC REVIEW 6 Drafts of the ISA will be reviewed by the CASAC Pb Review Panel and made available 7 for public comment, as indicated in Figure 4-1 a bove. The CASAC Pb Revi ew Panel will review 8
the first draft ISA and discuss their comments in a public meeting announced in the Federal 9 Register. Based on CASAC’s past practice, EPA anticipates that key CASAC advice and 10 recommendations for revision of the first draft ISA will be summarized by the CASAC Review 11
Panel in a letter to the EPA Administrator. In revising the first draft ISA, EPA will take into 12 account any such recommendations. EPA will al so consider comments received from CASAC 13 or from the public at the meeti ng itself and any written public comments. Additionally, EPA has 14 established a public docket for development of the ISA. 16 EPA will prepare a second draft ISA 15 for CASAC review and public comment. The CASA C Pb Review Panel will review the second 16 draft ISA and discuss their comments in a public meeting announced in the Federal Register. 17 Again, based on CASAC’s past practice, EP A anticipates that key CASAC advice and 18 recommendations for revision of the second draft ISA will be summarized by the CASAC Pb 19
Review Panel in a letter to th e EPA Administrator. In finalizing the ISA, EPA will take into 20 account any such recommendations. EPA will also c onsider comments received from CASAC or 21 from the public at the meeting itself and any written public comments. After appropriate 22 revision, the final document will be made public ly available on an EPA website and in hard 23 copy. A notice announcing the ava ilability of the final ISA w ill be published in the Federal 24 Register. 25
26

16 The ISA docket for the current Pb review is iden tified as EPA-HQ-ORD-2011-0051. The draft and final ISAs and CASAC letters will be placed into this docket by EPA and the public may submit materials to it for EPA consideration in development of the ISA. This docket an d the rulemaking docket described in chapter 7 below are publicly accessible at www.regulations.gov

.March 2011 5-1 Draft – Do Not Quote or Cite 

## 5 QUANTITATIVE RISK AND EXPOSURE 1 

## ASSESSMENTS 2

Quantitative risk and exposure assessments are generally designed to estimate human 3 exposure and health risk, as we ll as environmental exposures a nd risks, when appropriate. 4 Development of the risk/exposure assessments (R EAs) draws upon the information presented in 5 the ISA and its supplemental materials. This includes information on atmospheric chemistry, air 6 quality, human and environmental exposures, in cluding biokinetic information, and health and 7
welfare effects of concern. In particular, the availability ofconcentration-response and dose8 response data from the health and welfare eff ects literature influences the types of exposure 9 assessment and risk characterization that are pe rformed. The health a nd welfare assessments 10 focus on exposures and dose metrics that are cons istent with effects of concern, with available 11 measurement and modeled data, where appropriate, used to generate estimates of exposure. 12 Characterization of risks may include conducting air quality an alyses to support quantitative 13 exposure and risk assessments in specific locati ons to the extent warranted by new information, 14 taking into consideration availabl e resources. The results of such assessments are generally put 15 into a broader public health and public welfare perspective, for example, with a particular 16 emphasis on exposures and health risks in susceptible populations, such as children. 17 This phase generally begins with the prepara tion of a planning document. This document 18 considers the extent to which newly availabl e scientific evidence and tools/methodologies 19 provide support for conducting quantitative risk a nd exposure assessments. To the extent 20 warranted, the scope and methods for components of exposure/risk assessments are described. 21 This document is the subject of a consultation with the CASAC Panel and is made available to 22 the public for review and comment. If warrante d, one or more drafts of an REA are then 23 prepared and released for CASAC review and public comment prior to completion of a final 24 REA subsequent to completion of the final ISA. 25 The information newly available in this review is considered in light of the 26 comprehensive, complex and resource-intensive quantitative assessments of human exposure and 27 health risks performed for the last review. This information is considered with regard to the 28 extent to which it indicates the potential for development of an REA fr om which substantially 29 different conclusions might be drawn with regard to the health risks associated with air-related 30 Pb under conditions associated with the current standard. The REA planning document will 31
describe this consideration of the available sc ientific evidence, tool s and methodologies by EPA 32 staff in light of areas of uncertainty in the REA prepared for the last review and of the potential 33 for a new REA to provide notably different exposu re and ris k estimates, with lower associated 34March 2011 5-2 Draft – Do Not Quote or Cite uncertainty. The timeline for collection of am bient air Pb data under the recently revised 1 monitoring requirements is also recognized as a consideration fo r this document. Consultation 2
with the CASAC Pb Panel and comments from th e public on this draft IRP, as well as the 3 availability of resources, will also inform development of the REA planning document. 4



### 5.1 OVERVIEW OF ASSESSMEN TS IN LAST REVIEW 5 In the last review, EPA designed and devel oped a full-scale human exposure and health 6 risk assessment as well as a screening-level eco logical risk assessment. These assessments are 7
summarized below. 8



### 5.1.1 Human Exposure and Health Risk Assessments 9
In the last review, EPA deve loped and applied models to estimate human exposures to 10
air-related Pb and associated health risk. Es timates were developed for various air quality 11 scenarios and alternative standards to provide ad ditional information and insights that could help 12 to put judgments about risk associated with exposure to air-related Pb in a broader public health 13
context and inform decisions on the standards. The exposure and risk anal yses to estimate blood 14 Pb and associated IQ loss in children exposed to air-related Pb were cond ucted in the context of 15 five case studies that generally represent two types of population exposures: (1) more highly air16 pathway exposed children (as described below) residing in small ne ighborhoods or localized 17
residential areas with air concentrations somewh at near the standard being evaluated, and (2) 18 location-specific urban populati ons with a broader range of ai r-related exposures. The case 19 studies representing the more highly air-pathway exposed children included a general urban case 20 study and a primary Pb smelter case study. Th e three location-specific urban case studies 21 focused on specific residential areas within three U.S. cities to provide representations of urban 22 populations with a broader range of air-related exposures due to sp atial gradients in both ambient 23 air Pb levels and population density. The air qua lity scenarios assessed included (a) the current 24 NAAQS (for all five case studies ) ; (b) current conditions for the location-specific and general 25 urban case studies (which are below the current NAAQS); and (c) a range of alternate standard 26 levels (for all case studies). 27 Exposure and associated blood Pb levels were simulated using the Integrated Exposure 28 and Uptake Biokinetic (IEUBK) model, as more fully described and presented in the Risk 29 Assessment Report (USEPA, 2007a). The assess ment incorporated a number of innovative 30 design elements intended to support a probabilistic characterization of risk with consideration for 31 the multi-pathway nature of lead exposure. In generating risk estimates, empirical data were 32 combined with mechanistic modeling to increase the representativeness of the risk estimates 33 generated. Some of the more important design elem ents included in the risk model were: (a) use 34 of monitor data as the basis for characterizing Pb levels in ambient air for the case studies and in 35March 2011 5-3 Draft – Do Not Quote or Cite outdoor soil, (b) use of a combination of empiri cally-derived ratios and more complex empirical1 mechanistic hybrid modeling to predict indoor dust Pb levels associated with ambient (outdoor) 2
air Pb levels and Pb levels in other related me dia such outdoor soil, (c) use of empirical data 3 characterizing Pb exposure for some pathways su ch as dietary intake, (d) use of IEUBK to 4 predict central tendency blood Pb (PbB) levels for study populations given pathway-specific 5 intake rates (e) use of empirica l PbB variability data combined with the IEUBK-based estimates 6 of central-tendency PbB levels to generate popula tion distributions of PbB levels and (f) use of 7 epidemiological study-based concentration-response functions for IQ loss in children (given 8 specified PbB levels) to generate risk distributions. The risk model that was developed allowed 9 us to estimate IQ loss estimates for various pe rcentiles of each study population and furthermore, 10 to partition that risk between various pathways of interest (although w ith varying degrees of 11 overall confidence, as noted below). 12 Although the assessment utilized a number of innovative modeling elements in order to 13 generate representative estimates of risk for our study populations, like all risk models there was 14 uncertainty associated with the model and its out put. For example, because of the evidence for a 15 nonlinear response of blood Pb to exposure and also the nonlinearity reflected in the C–R 16 functions for estimation of IQ loss, the assessm ent first estimated total blood Pb levels and 17 associated risk (i.e., for air- and nonair-related exposure pathways), and then separated out those 18
estimates of blood Pb and associated risk associated with the pathways of in terest in this review. 19 We separated out the estimates of total (all -pathway) blood Pb and IQ loss into a background 20 category and two air-related cate gories. However, significant limitations in our modeling tools 21 and data resulted in an inability to parse specific risk estimates into specific pathways, such that 22 we approximated estimates for th e air-related and b ackground categories. We believe these 23 limitations led to slight overestimation of the ri sks in the one of the air-related categories and 24 under representation of air-related pathways in the second category. Thus, we characterized the 25 risk attributable to air-related exposure path ways to be bounded by the estimates developed for 26 the two air-related categories. 27 Additional limitations, assumptions and uncerta inties, which were recognized in various 28 ways in the assessment and presen tation of results, are listed be low, beginning with those related 29 to design of the assessment or case studies, fo llowed by those related to estimation of Pb 30 concentrations in ambient air, indoor dust, out door soil/dust, and blood, and estim ation of Pb31 related IQ loss. 32

 Temporal Aspects: During the 7-year exposure period, media concentrations remain 33 fixed and the simulated child remains at the same residence (while exposure factors and 34 physiological parameters are adjusted to match the age of the child). 35March 2011 5-4 Draft – Do Not Quote or Cite  General Urban Case Study: The design for this case study employs assumptions 1 regarding uniformity that are reasonable in the co ntext of a small neighborhood 2 population, but would contribute uncertainty to extrapolatio n of these estimates to a 3 specific urban location, particular ly a relatively large one. 4

 Location-specific Urban Case Studies: Limitations in the ambient air monitoring 5 network limit characterization of spatial gradie nts of ambient air Pb in these case studies. 6

 Air Quality Simulation: The proportional roll-up and roll-down procedures used in some 7 case studies to simulate the then-current NAAQS and alternate NAAQS levels, 8 respectively, assume proportional changes in air concentrations across the study area in 9 those scenarios for those case studies. 10

 Outdoor Soil/Dust Pb Concentrations: Uncerta inty regarding soil/dust Pb levels and the 11 inability to simulate the influence of cha nging air Pb levels related to lowering the 12 NAAQS contributes uncertainty to air-related risk estimates. 13

 Indoor Dust Pb Concentrations: Limitations and uncertainty in modeling of indoor dust 14 Pb levels, including the impact of reductions in ambient air Pb levels, contributes 15 uncertainty to air-related risk estimates. 16

 Interindividual Variability in Blood Pb Levels: Uncerta inty related to population 17 variability in blood Pb levels, and limitati ons in our ability to model it, introduces 18 uncertainty into blood Pb and IQ loss estimates for the 95 th percentile of the population. 19

 Pathway Apportionment for Higher Percentile Blood Pb and IQ Loss: Limitations in 20 data, modeling tools and assessment design intr oduce uncertainty into estimates of air21 related blood Pb and IQ loss for the upper ends of population distribution. 22

 IQ Loss Concentration-response Functions: Specification of the quantitative relationship 23 between blood Pb level and IQ loss is subjec t to significant uncertainty at lowest blood 24 Pb levels (e.g., below 5 μg /dL concurrent blood Pb). 25 The assumptions, limitations and uncertainties noted above are areas for consideration as 26 to any advances in available data and or risk characterization met hods with regard to the extent 27 to which they might substantially address areas of largest uncertainty with regard to estimation of 28
health risks associated with ambient air-related Pb. 29

30March 2011 5-5 Draft – Do Not Quote or Cite 

### 5.1.2 Ecological Risk Assessment 1
A screening level risk assessment was perfor med by EPA for the last review to estimate 2 the potential for ecological risks associated w ith exposures to Pb emitted into ambient air. 17 This 3 assessment built upon the environmental concentr ations modeling performed for the human 4 exposure and health risk assessment described above. A case study approach was used which 5 included areas surrounding a primary Pb smelter and a secondary Pb smelter, as well as a 6 location near a nonurban roadway. Soil, surface wa ter, and/or sediment concentrations were 7
estimated for each of the three in itial case studies from available monitoring data or modeling 8 analysis, and then compared to ecological scr eening benchmarks to assess the potential for 9 ecological impacts from Pb that was emitted into the air. A national-scale screening assessment 10
was also used to evaluate surface water and sediment monitoring locations across the United 11 States for the potential for ecological impacts asso ciated with atmospheric deposition of Pb. All 12
three case studies and the national-scale assessmen t considered current or recent environmental 13 conditions. In all cases but the primary Pb sme lter case study, current air quality conditions were 14 below the then-current NAAQS. The current ai r quality conditions for the primary Pb smelter 15 case study exceeded the NAAQS. An additional case study was identified to look at gasoline16 derived Pb effects on an ecologically vulnerable ecosystem but various limitations precluded any 17 analyses. 18 Ecological screening values, develope d from the Eco-SSLs methodology, EPA’s 19 recommended ambient water quality criteria, an d sediment screening values developed by 20 MacDonald and others (2000, 2003) were used to estimate the potential for ecological risk. A 21 Hazard Quotient (HQ) was calculated for various r eceptors to determine the potential for risk to 22 that receptor. The HQ was calculated as the ratio of the media concentra tion to the ecotoxicity 23 screening value. For each case study, HQ values were calculated for each location where either 24
modeled or measured media concentrations were available. Separate soil HQ values were 25 calculated for each ecological receptor group for wh ich an ecotoxicity screening value has been 26 developed (i.e., birds, mammals, soil invertebrate s, and plants). HQ values less than 1.0 were 27 concluded to suggest that Pb concentrations in a specific medium were unlikely to pose 28 significant risks to ecological receptors, while HQ values greater than 1.0 indicated that the 29 expected exposure exceeded the ecotoxicity screen ing value, which was concluded to indicate a 30 potential for adverse effects. 31 Several uncertainties that apply across case studies were identified: 32

17 The assessment is described in detail in Lead Human Exposure and Health Risk Assessments and Ecological Risk Assessment for Sel ected Areas, Pilot Phase (ICF, 2006 ). Various limitations precluded performance of a full-scale ec ological risk assessment.March 2011 5-6 Draft – Do Not Quote or Cite  The ecological risk screen was limited to spec ific case study locations and other locations 1
for which Pb data were available. Efforts were made to ensure that the Pb exposures 2
assessed were attributable to airborne Pb and not dominated by nonair sources. However, 3 there was uncertainty as to whether other s ources might have actually contributed to the 4 Pb exposure estimates. 5

 A limitation to using the selected ecotoxicity sc reening values is that they might not be 6 sufficient to identify risks to some thr eatened or endangered species or unusually 7 sensitive aquatic ecosystems (e.g., 2006 AQCD, p. AX7–110). 8

 The methods and database from which the surface water screeni ng values (i.e., EPA9 recommended ambient water quality criteria fo r Pb) were derived is somewhat dated. 10 New data and approaches (e.g., use of pH as indicator of bioava ilability) may now be 11 available to estimated the aquatic toxici ty of Pb (2006 AQCD, sections X7.2.1.2 and 12 AX7.2.1.3). 13

 No adjustments were made for sediment-speci fic characteristics that might affect the 14 bioavailability of Pb in sediments in the deri vation of the sediment quality criteria used 15 for this ecological risk screen (2006 AQCD, sections 7.2.1 and AX7.2.1.4; Appendix M, 16 ICF, 2006). Similarly, characteristics of so ils for the case study locations were not 17 evaluated for measures of bioavailability. 18

 Although the screening value for birds used in this analysis is based on reasonable 19 estimates for diet composition and assimilati on efficiency parameters, it was based on a 20
conservative estimate of the relative bioava ilability of Pb in soil and natural diets 21 compared with water soluble Pb added to an experimental pellet diet (Appendix L, ICF, 22 2006). 23 For the case studies, the concentrations of Pb in soil and sediments in various locations 24 exceeded screening values for these media indicati ng potential for adverse effects to terrestrial 25 organisms (plants, birds and mammals) and to sediment dwelling organisms. While the 26 assessment was limited in that it was not possible to dissect the contributions of air Pb emissions 27 from other sources, it is likely that, at least for the primary smelter, that the air contribution is 28 significant. For the other case studies, the cont ributions of current air emissions to the Pb 29 burden, is less clear. Th e nationa l-scale screen of surface water data initially identified 15 areas 30
for which water column levels of dissolved Pb were greater than hardness adjusted chronic 31 criteria for the protection of aqua tic life indicating a potential for a dverse effect if concentrations 32 were persistent over chronic periods. Acute criteri a were not exceeded at any of these locations. 33
The extent to which air emissions of Pb had cont ributed to these surface water Pb concentrations 34
is unclear. In the national-scale screen of se diment data associated with the 15 surface water 35 sites described above, threshold effect concentra tion-based HQs at nine of these sites exceeded 36March 2011 5-7 Draft – Do Not Quote or Cite 1.0. Additionally, HQs based on probable effect con centrations exceeded 1.0 at five of the sites, 1 indicating probable adverse effects to sediment dwelling organisms. Thus, sediment Pb 2 concentrations at some sites are high enough th at there is a likelihood that they would cause 3
adverse effects to sediment dwel ling organisms. However, the contribution of air emissions to 4
these concentrations is unknown. 5



### 5.2 CONSIDERATION OF QUANTITATI VE ASSESSMENTS FOR THIS 6 

### REVIEW 7

To the extent that new research and/or im proved methodologies are identified to inform 8 updates to the design of Pb exposure and risk asse ssments or new scientific evidence is available 9 to substantially inform our ability to characte rize and/or reduce uncertainties identified in the 10 assessments performed for the last revi ew, EPA may design and conduct quantitative 11 assessments for this review. Drawing on the ev aluation of evidence in the first draft ISA, a 12 planning document will systematically discuss the available scientific evidence, tools and 13 methodologies pertaining to each of the key aspects of an assessment, with particular attention to 14 evidence and tools newly available in this review . This discussion will focus particularly on 15 areas of uncertainty in the REA prepared for th e last review and the pot ential for a new REA to 16 provide notably different exposure and risk estimates, w ith lower associated uncertainty. Some 17 key areas for staff analysis, including types of data, methodology and tools to be considered, are 18
summarized below. 19



### 5.2.1 Human Exposure and Health Risk Assessments 20

5.2.1.1 Air Quality and Environmental Media Concentrations 21
Generally speaking, and as addressed in the la st review, Pb concentrations in air and 22 indoor dust, and to some extent outdoor dust/ soil, are particularly key components in the 23
assessment of air-related Pb health risk. In th e case studies included in the assessment for the 24 last review, a mixture of mode ling and monitoring approaches we re used to estimate these 25 concentrations. For example, in the location-specif ic urban case studies, air concentrations were 26 estimated based on the assignment of ambient m onitor concentrations to U.S. Census units 27 according to proximity. The limited number of monitors in relation to sources contributed 28 uncertainty to our characterizati on of spatial gradients in ambien t air concentration. Limitations 29 and uncertainty in modeling the a ssociated Pb concentrations in indoor dust was another area of 30 uncertainty. In considering the extent to whic h new information or insights might be gained 31 from a new assessment, we will consider the avai lability of new information or methods in these 32

areas. 33March 2011 5-8 Draft – Do Not Quote or Cite To the extent more spatially detailed information on air Pb concentrations in the urban 1 context is available, this could reduce this ar ea of uncertainty in the risk assessment completed 2 for the last review. Specifically, more spat ially-refined air concentration estimates or 3 measurements might allow us to more accura tely define spatial gradients around ambient 4 monitors, potentially differentiating gradients around source-oriented monitors from those 5
associated with nonsource oriented monitors. Th is might in turn improve the representativeness 6
of the characterization of ambient air Pb con centrations for exposed populations in urban study 7 areas. If these types of more refined ambient data are available, an initial step to consider the 8 impact of their inclusion in the assessment could be a sensitivity analysis -oriented calculation for 9 one study area to determine the degree to which this type of refined ambient Pb spatial gradient 10 data could impact exposure (and ultimately risk) estimates. 11 An additional area of uncertainty recognized in the last assessment concerned the 12 procedures for simulating conditions for alterna tive NAAQS levels. The av ailability of more 13
refined ambient air Pb data or other informa tion providing insights into the spatial pattern 14 associated with reductions in ambient Pb levels (i .e., spatial pattern of rollbacks in ambient air Pb 15 levels) could address another importa nt source of uncertainty with regard to estimation of air Pb 16 concentrations in the previous risk assessment. 17 With regard to media related to indoor dust Pb modeling, any newly available urban 18
residential datasets with matched measurements useful in evaluating the relationship between 19 ambient outdoor air Pb and indoor dust Pb may be important to consider with regard to 20
evaluation of this source of un certainty in the risk assessment completed for the last review. 21 Specifically, having outdoor ambient air Pb data matched to outdoor soil Pb, indoor ambient air 22 Pb and indoor dust Pb data, for a set of reside ntial locations, might improve our ability to 23 evaluate and possibly further calibrate perf ormance of the hybrid indoor dust Pb model 24 developed and used in the last review. The availability of multiple matched media 25 concentrations over an extended period (e.g., allo wing for characterization of daily, weekly or 26 monthly levels) would further improve their utility in this regard. This reflects the fact that the 27 dust Pb model is a dynamic model which combin es mechanistic and empirical elements to 28 generate a near-steady state estimate of indoor dust Pb con centrations given various loading 29 rates. Therefore, having data which are temporal ly refined would allow us to evaluate the degree 30 to which the model tracks the temporal profile of these media concentrations. 31
The characterization of soil Pb levels and their relationship to air Pb levels, particularly in 32 urban areas is another area contributing to the exp osure characterization in which uncertainty 33 might be reduced with new information or methods. For example, the identification of more 34 current data characterizing Pb soil levels in the urban residential context which could be further 35 differentiated to capture any regi onal trends and potentially mo re importantly, differences in 36March 2011 5-9 Draft – Do Not Quote or Cite housing age (as a surrogate for information on leaded paint usage) might further reduce 1 uncertainty associated with modeling this pathwa y, characterizing contribu tions from air-related 2 and nonair-related sources, and potentially in modeling total exposur e and total risk. 3 Considering housing age in characterizing outdoor so il Pb levels is potentially important because 4 in some cases (i.e., older houses with Pb exterior paint), soil Pb levels can be elevated due to 5 historical loading from weathere d exterior Pb paint. Furtherm ore, older houses are also more 6 likely to have higher concentrations of indoor dust Pb contributed by older indoor Pb paint. 7 Together these two factors mean that background (nonair) exposures to Pb can be elevated for 8 residents of older houses, a factor important to re flect in our risk assessment to the extent that 9
data allow. 10 An additional policy-relevant aspect of the environmental characterization component of 11
the last assessment concerned the identificati on of air-related and nonair-related (background) 12 environmental Pb concentrations. For example, as described in the documents prepared for the 13 last review, while conceptually indoor Pb pa int contributions to i ndoor dust Pb would be 14 considered nonair or background, technical limitations precluded us from parsing out the indoor 15 paint contributions from hi storic air-related Pb inindoor dust (73 FR 66980). 18 Similarly we 16 were unable to separate the ai r contribution to dietary or dr inking water Pb from the nonair 17 contributions, such that Pb in these pathways was identified as “background” yet recognized 18 qualitatively to also include ai r-related Pb. The availability of information and methods that 19 might improve our characterization of distinctions between these air and n onair-related pathways 20 will also be an important consideration with re gard to the potential for impact on REA results. 21

5.2.1.2 Human Exposure Assessment 22
The exposure assessment completed as part of the risk assessment for the last review 23 focused on characterizing population-level distributions of blood Pb levels, including (a) 24 estimates of high-end percentile estimates of that distribution and (b) estimation of the 25 apportionment of total PbB levels associated wi th a given percentile among air- and nonair26 related pathways of Pb. As not ed in the last review and earli er in this section, there is 27 considerable uncertainty associated with appor tioning total Pb exposure (a nd hence total risk) to 28 the air- and nonair-related pathways. 29 One aspect of the uncertainty in appo rtioning exposure and risk among exposure 30 pathways concerns uncertainty regarding the specific contribution of different Pb exposure 31 pathways to total exposure for individuals with widely differing total exposure. In the last 32 assessment we applied the same relative contri butions to all individua ls in the population. 33

18 Indoor dust Pb derived from lead r ecently emitted to the air was quantif ied separate from this combined historic Pb of paint or air origin.March 2011 5-10 Draft – Do Not Quote or Cite Uncertainty in this area reflect s the fact that we do not have comprehensive data on exposure 1 levels matched with PbB measurements for a larg er set of individuals, which prevents us from 2 assessing how contributions of different Pb e xposure pathways to total PbB may vary across 3 percentiles in the population distribu tion (of total PbB). If such da ta are now available, we could 4 be in a position to reduce this potentially important source of uncertainty. These types of data 5
could take the form of matched data on PbB le vels and dietary exposure (for a set of study 6 subjects). 7 Furthermore, we plan to consider the exte nt to which data are now available that 8 characterize key areas of variab ility in the inputs to modeli ng total PbB levels (e.g., soil Pb, 9 outdoor and indoor dust Pb, dietar y food Pb) which might support a probabilistic simulation of 10 the full range of exposure and risk for a given study population. An important aspect to this 11
consideration will be the availability of data characterizing the degree of correlation between 12 these modeling inputs (e.g., degree to which indoor dust Pb levels and outdoor soil Pb levels are 13 correlated). As available, the extent to which these types of data char acterizing variability in 14 pathway-specific Pb concentrations (and correlat ions between those distributions) might provide 15
the basis for a Monte Carlo simulation-based esti mation of population variability in PbB levels 16 with pathway apportionment for the simulated PbB le vels will also be considered, with regard to 17 the ability to estimate, for example, the 95 th population percentile PbB le vels and the fractional 18 contribution to that PbB level by the underlyi ng Pb exposure pathways. Another area for 19 consideration with regard to population variabil ity will be the availabi lity of more recent 20 information on PbB variability in study populat ions relevant for an assessment (e.g., the 21 availability of an updated estimate of populati on PbB variation such as geometric standard 22 deviation, potentially differentiated by region and possibly by housing stock or by the SES 23
attributes of the underl ying study population). 24

5.2.1.3 Health Risk Assessment 25
In analyzing newly available information pertai ning to the health risk assessment step, we 26 plan to consider newly available studies with regard to the support they might provide for 27 assessment of health endpoints and risk metrics other than childhood IQ and, as available, the 28 extent to which they indicate th e potential to lead to risk esti mates for notably different from 29 those of the last assessment. Focusing specifica lly on the step of translating childhood exposure 30 estimates into IQ loss estimates, as the risk metric, a key source of uncertainty in the last 31 assessment was the specification of the IQ loss function, specifically, th e portion of the function 32 predicting IQ loss at lower exposur e levels (e.g., below PbB levels of approximately 3-5 ug/dL). 33 If we identify either new cohort studies, or pooled/meta analyses based on existing studies which 34
describe the nature of the functi on at these lower exposure levels, then we might be in a position 35March 2011 5-11 Draft – Do Not Quote or Cite to reduce uncertainty in the risk assessment. To the extent such newly available information is 1 identified, we will consider the potential fo r it to impact REA re sults and the size and 2 characterization of such impact. One other source of uncertainty that might be reduced with new 3 information, involves the type of PbB metric to use (concurrent, lifetim e averaged etc). For 4 example, if newly available study da ta clearly point to the importan ce of a PbB metric other than 5
the concurrent metric used in the last review, then, depending on the associated concentration6 response function, this could impact the risk estimates generated. 7



### 5.2.2 Ecological Risk Assessment 8
In considering the extent to which the currently available information warrants 9 development of an ecological risk assessment in this review, we will consider both the 10 availability of new air quality data and data or estimates for other media that might inform 11 consideration of the current Pb standards, as we ll as any newly available scientific evidence that 12 indicates a more refined understanding of the dire ct and indirect effects of deposited ambient Pb 13 on ecosystems and organisms. We intend to focus most specifically on 1) the ability of current 14 data sets to characterize exposur e of ecosystems to ambient Pb currently being deposited and 2) 15 any new evidence that would allow the current review to arrive at different conclusions as to the 16 causality or degree of eff ect than the last review. 17 In considering air quality information, availa bility of monitoring data from the newly 18 designed Pb monitoring network, discussed below in chapter 6, will be considered. For example, 19 available ambient data may be evaluated with re gard to its adequacy for determining ambient 20 concentrations of Pb in potenti ally vulnerable ecosystems. Th e availability of methods or 21 models to estimate the amount of deposition occurri ng in those areas will also be considered. 22 Additionally, it will be important to consider the available information with regard to its 23 usefulness for apportioning source s of deposited Pb to ambient sources (as compared to nonair 24 sources of Pb in ecosystems). A key consideration will be with regard to the extent to which 25 information is available to support a quantitat ive analysis of ambien t Pb-related effects 26
associated with current ambient conditions or at conditions meeting the current standard. 27 In the last review, the scientific evidence of direct effect from current ambient levels of 28 Pb to specific ecosystems or organisms was limite d. In considering the scientific evidence on 29 which a risk assessment might be based, staff pl ans to evaluate whether there is sufficient 30 scientific evidence to causally link deposited at mospheric lead with adverse ecological effects 31
under the current standard. Info rmation relating to critical lo ads for Pb in ecosystems was 32 lacking in the last review. Staff plans to evalua te the adequacy of any ne w scientific evidence on 33 critical loads that might be used in assessing ecosystems poten tially vulnerable to Pb on a 34 national-scale. Staff also plans to look at any new scientific evidence that might be available to 35March 2011 5-12 Draft – Do Not Quote or Cite apportion specific ecological effects to ambient air Pb as opposed to other sources of current and 1 historic Pb in the environment, as well as to pr ovide additional insight into the responsiveness of 2 ecosystems to changes in Pb deposition. 3



### 5.3 SCIENTIFIC AND PUBLIC REVIEW 4 The REA planning document will be distributed to the CASAC Pb Panel for their 5 consideration and provided to the public for review and comment. The document will be the 6 subject of a consultation with the CASAC Pb Pane l at a public meeting that will be announced in 7 the Federal Register. 8 If upon consideration of CASAC and public co mments, EPA concludes that development 9 of a new REA, or updating or expanding the last assessment, is warranted, staff will take into 10
account comments received from CASAC and the public in designing and conducting the 11 assessments. In such a case, staff would prepare at least one draft of th e assessments for CASAC 12 review and public comment. Review would be conducted by the CASAC Pb Review Panel and 13 discussed at public meetings that would be announced in the Fe deral Register. Based on past 14 practice by CASAC, EPA expects that key advice and recommendations for revision of the 15
document would be summarized in a letter to th e EPA Administrator. In revising the draft REA 16 document, EPA would take into account any such recommendations, and also consider 17 comments received, from CASAC or from the p ublic, at the meeting itself and any written 18 comments received. A final document would then be made available on an EPA website, with 19 its public availability announced in the Federal Register. 20 If upon consideration of CASAC and public comments on the REA planning document, 21 EPA concludes that development of a new REA is not warranted, a REA will not be developed 22 and the Policy Assessment for this review will draw from the REA developed in the last review 23 in light of analyses or assessments made in the REA planning documen t with regard to the 24 current evidence pertaining to exposure and risk, as well as the evidence presented in the ISA 25 and other documents prepared for the review. Review steps for the PA are described in section 26
7.1 below. 27March 2011 6-1 Draft – Do Not Quote or Cite 

## 6 AMBIENT AIR MONITORING CONSIDERATIONS 1

In the course of NAAQS reviews, aspects of the methods for sampling and analysis of the 2 NAAQS pollutant are reviewed, and the curren t network of monitoring locations with the 3
associated data is considered. The methods for sampling and analysis of each NAAQS pollutant 4 are generally reviewed in conjunction with c onsideration of the indicator element for each 5 NAAQS. Consideration of the ambient air monitoring network generally informs the 6 interpretation of current data on ambient air co ncentrations, and helps identify if the monitoring 7 network is adequate to determine compliance with a potentially revised Pb NAAQS. This 8 chapter describes plans for considering these aspects of the ambient ai r monitoring program for 9
Pb. 19 10 

### 6.1 CONSIDERATION OF SAMPLI NG AND ANALYSIS METHODS 11
In order to be used in attainment designations, ambient Pb concentration data must be 12 obtained using either the Federal Reference Method (FRM) or a Federal Equivalent Method 13 (FEM). As described in section 1.3 above, the in dicator for the current Pb NAAQS is Pb-TSP. 14 However, in some situations (described below), ambient Pb-PM 10 concentrations may be used in 15 judging nonattainment. Accordingly, FRMs have been established for Pb-TSP and for Pb-PM 10
. 16 The current FRM for the measurement of Pb-TSP is provided in 40 CFR part 50 17 Appendix G. This FRM includes sampling usin g a high-volume TSP sampler that meets the 18 design criteria identified in 40 CF R part 50 Appendix B and sample analysis for Pb content using 19 flame atomic adsorption. There are 24 FEMs currently approved for Pb-TSP. 20 All 24 FEMs are 20 based on the use of high-volume TSP samplers a nd a variety of approved equivalent analysis 21
methods. 22 During the review of the Pb NAAQS completed in 2008, CASAC noted the variability in 23 high-volume TSP sample measurements associat ed with the effects of wind speed and wind 24 direction on collection efficiency in their commen ts regarding the indicator. However, at the 25 time of the 2008 review, no alternat ive TSP sampler designs were id entified that had an adequate 26
characterization of their collection efficiency over a wide rang e of particle sizes. The existing 27 high volume sampler was retained as the sampling approach for the Pb-TSP FRM and FEMs. 28

19 The code of federal regulations (CFR) at parts 50, 53 and 58 specifies required aspects of the ambient monitoring program for NAAQS pollutants. The federa l reference methods (FRMs) for sample collection and analysis are specified in 40 CFR part 50, the procedures for approval of FRMs and federal equivalent methods (FEMs) are specified in 40 CFR part 53 and the rules specifying requirements for the planning and operations of the ambient monitoring network are specified in 40 CFR part 58.

20 A complete list of FEM can be found at the following webpage - http://www.epa.gov/ttn/am tic/files/ambient/criteria/refere nce-equivalent-methods-list.pdfMarch 2011 6-2 Draft – Do Not Quote or Cite Due to reduced availability of laborator ies capable of performing flame atomic 1 adsorption analyses and general a dvances in analysis methods, the EPA has initiated an effort to 2 replace atomic adsorption with a more modern analysis method such as inductively coupled 3 plasma mass spectroscopy (ICP-MS ). A consultation with th e CASAC Ambient Air Monitoring 4 and Methods Subcommittee was held on September 15, 2010 and the EPA plans to propose a 5 new FRM based on a more modern analysis method in the fall of 2011. 6 In addition to maintaining the existing FRM for Pb-TSP, a new FRM for Pb in PM 10 (Pb7

PM 10 ) was promulgated as part of the 2008 re view. This new FRM is based on the PM 10 sampler 8 defined in 40 CFR part 50 Appendix J coupled w ith x-ray fluorescence (XRF) analysis. The Pb9

PM 10 measurements may be used as an alternativ e to Pb-TSP measurements in certain conditions 10 defined in 40 CFR part 58 Appendix D paragr aph 2.10.1.2. These conditions include where Pb 11 concentrations are not expect ed to equal or exceed 0.10 micr ograms per cubic meter on an 12
arithmetic 3-month mean and wher e the source of Pb emissions is expected to emit a substantial 13 majority of its Pb in the PM 10 size fraction. 14 Sampling and analysis issues to be consider ed during this review include the following: 15

 Are new TSP samplers available and adequately characterized for use in Pb-TSP 16 sampling? 17

 Are new data on Pb size distribut ions available that would bett er inform the need for Pb18 TSP or the adequacy of Pb measurements in PM 10 or other size fractions (e.g., Pb-PM 15 19 or Pb-PM 20 ) in characterizing total Pb concentrations? 20

 If an alternative size fraction is identified that may adequately characterize total Pb 21 concentrations, are there samplers for that size fraction that have been adequately 22 characterized that can be used as th e basis for a new FRM sampling method? 23

24 

### 6.2 CONSIDERATION OF AIR MONITORING NETWORK 25 

### REQUIREMENTS 26
The majority of data used to determine compliance with the Pb NAAQS are obtained 27 from monitors operated by state, local, and trib al monitoring agencies (“monitoring agencies”). 28 These monitors are either required due to fede ral regulations (40 CFR part 58, Appendix D) and 29 state regulations, or are operated voluntarily by the monitoring agency. A review of the 30 available lead monitoring data and then-existin g Pb monitoring network was performed as part 31 of the 2008 Pb NAAQS review (USEPA, 2007b). Th is review indicated that the Pb monitoring 32 network existing at that time was inadequate to assess compliance and determine the extent of all 33 the areas that may violate the revised NAAQS. Many states had no ambient air Pb monitors in 34 place, such that there were large portions of th e country with no data being collected on Pb 35 concentrations in ambient air. In addition, many of the largest Pb emitting sources in the country 36March 2011 6-3 Draft – Do Not Quote or Cite did not have nearby ambient Pb air monitors. Due to these findings, the EPA promulgated 1 revised Pb monitoring network design requirements along with the revised Pb NAAQS (73 FR 2 66964). The Pb monitoring network design requir ements were revised again in December 2010 3 as a result of EPA’s decision to grant a peti tion to reconsider the prior network design 4 requirements that was filed by several environm ental and public health organizations (75 FR 5 81126). 6 The current Pb monitoring network design re quirements (40 CFR part 58, Appendix D, 7 paragraph 4.5) include two types of monitoring sites – source-oriented monitoring sites, and non8 source-oriented monitoring sites. Source-oriented monitoring site s are required near sources of 9 air Pb emissions which are expected to or have been shown to contri bute to ambient air Pb 10 concentrations in excess of the NAAQS. At a minimum, there must be one source-oriented site 11
located to measure the maximum Pb concentration in ambient air resulting from each non-airport 12 Pb source which emits 0.50 or more tons of Pb pe r year and from each airport which emits 1.0 or 13 more tons of Pb per year. 21 In addition, one year of mon itoring is required near 15 specific 14 airports in order to gather additional inform ation on the likelihood of NAAQS exceedances near 15 airports due to the combustion of leaded aviation gasoline (75 FR 81126). 16 Monitoring agencies are required to conduct non-source-oriented Pb monitoring at the 17 multipollutant monitoring sites (referred to as NCore sites, required under 40 CFR part 58 18 Appendix D, paragraph 3) in Core Based Sta tistical Areas (CBSA) with a population of 500,000 19

or more. 22 While non-source-oriented monitoring data can be used for designation purposes, the 20 main objective for non-source-oriented monitoring is to gather information on neighborhood21
scale lead concentrations that are typical in urban areas so to better understand ambient air22 related Pb exposures fo r the general population. 23 Following the implementation of the December 2010 Pb network requirements, the Pb 24 monitoring network will consist of approxi mately 270 required monitors including 25 approximately 210 source-oriented monitors a nd 60 non-source-oriented monitors. Figure 6.1 26 shows the estimated geographic distribution of mon itors associated with these new requirements. 27

21 The Regional Administrator may waive the requirement in paragraph 4.5(a) for monitoring near Pb sources if the State or, where appropriate, local agency can demonstrate the Pb source will not contribute to a maximum Pb concentration in ambient air in excess of 50 percent of the NAAQS (based on historical monitoring data, modeling, or other means).

22 Defined by the US Census Bureau - http://www.c ensus.gov/population/www/metroareas/metroarea.htmlMarch 2011 6-4 Draft – Do Not Quote or Cite 1

Figure 6-1. Map of Required Lead Monitors based on 2005 National Emission Inventory Estimates. 2 Sampling and analysis issues to be consider ed during this review include the following: 3

 Is the current emission threshol d of 0.50 tons per year for in dustrial sources and 1.0 tons 4 per year for airports appropriate and ade quate for determining compliance with the 5 current or alternative NAAQS considered? 6

 The current monitoring requirements specify source emissions thresholds intended to 7 identify situations where these emissions may result in exceedances of the current 8 NAAQS (e.g., near stationary sources or airports) and also provide for the identification 9 of areas of historic industr ial activity from which emissions may also result in 10 exceedances. Is there recent, newly availa ble information indicating other situations 11 where exceedances to the current NAAQS are likely to occur? To the extent that 12 revisions to the NAAQS are considered during this review, at what alternative levels 13 and/or averaging times would other types of Pb sources be likely to cause exceedances to 14 the alternative NAAQS considered? 15

16
17March 2011 7-1 Draft – Do Not Quote or Cite 

## 7 POLICY ASSESSMENT AND RULEMAKING 1



### 7.1 POLICY ASSESSMENT 2 The PA, like the previous OAQPS Staff Paper, is a document that provides a transparent 3 OAQPS staff analysis and staff conclusions regarding the adequacy of the current standards and 4 potential alternatives that are a ppropriate to consider prior to th e issuance of proposed and final 5 rules. The PA integrates and interprets the in formation from the ISA and REA(s) to frame policy 6 options for consideration by the Administrator. The PA is also intended to facilitate CASAC’s 7 advice to the Agency and recommendations to th e Administrator on the ad equacy of the existing 8 standards or revisions that may be appropriate to consider, as provi ded for in the Clean Air Act. 9
Staff conclusions will be based on the informati on contained in the ISA, and, as available, the 10
REA 23 , and any additional staff eval uations and assessments discu ssed in the PA. In so doing, 11 the discussion in the PA will be framed by cons ideration of a series of the policy-relevant 12 questions drawn from those outlined in chapter 3, including the fundamental questions associated 13 with the adequacy of the curre nt standards and, as appropriate , consideration of alternative 14 standards in terms of the specific elements of th e standards: indicator, av eraging time, level, and 15
form. 16 The PA will identify conceptual evidence-ba sed and risk/exposure-based approaches for 17 reaching public health and welf are policy judgments. It will discuss the implications of the 18 science and quantitative assessments for the adeq uacy of the current standards, and for any 19
alternative standards under consideration. The PA will also describe a broad range of policy 20 options for standard setting, identifying the broa dest range for which the staff identifies support 21 within the available information. In so doing, th e PA will describe the underlying interpretations 22
of the scientific evidence a nd risk/exposure information that might support such alternative 23 policy options that could be considered by the Administrator in making decisions for the Pb 24
standards. 25 In identifying a range of primar y standard options for the Admi nistrator to consider, it is 26 recognized that the final decision will be larg ely a public health policy judgment. A final 27 decision must draw upon scientific information a nd analyses about health effects and risks, as 28 well as judgments about how to d eal with the range of uncertainti es that are inherent in the 29 scientific evidence and analyses. Staff’s appro ach to informing these judgments is based on a 30 recognition that the available hea lth effects evidence generally reflects a continuum consisting of 31 ambient levels at which scientists generally agre e that health effects ar e likely to occur through 32

23 The quantitative risk and exposure assessments from the last review may be consid ered in light of current air quality analyses if new quantitative risk and expo sure assessments are not developed for this review.March 2011 7-2 Draft – Do Not Quote or Cite lower levels at which the likelihood and magn itude of the response become increasingly 1 uncertain. This approach is consistent with the requirements of the NAAQS provisions of the 2
Act and with how EPA and the courts have hist orically interpreted the Act. These provisions 3 require the Administrator to establ ish primary standards that are requi site to protect public health 4 and are neither more nor less stringent than ne cessary for this purpose. The provisions do not 5 require that primary standards be set at a zero-risk level, but rather at a level that avoids 6 unacceptable risks to public health, in cluding the health of sensitive groups. 24 7 In identifying a range of secondary standard options for the Administrator to consider, 8 staff recognizes that the final decision will be largely a public policy judg ment. A final decision 9 must draw upon scientific evidence and analyses about effects on public welfare, as well as 10 judgments about how to deal with the range of un certainties that are inhe rent in the relevant 11 information. This approach is consistent with the requirements of the NAAQS provisions of the 12
Act and with how EPA and the cour ts have historically interpreted the Act. These provisions 13 require the Administrator to esta blish secondary standa rds that are requisite to protect public 14 welfare from any known or anticipated adverse effects associated with the presence of the 15 pollutant in the ambient air. In so doing, the Ad ministrator seeks to esta blish standards that are 16 neither more nor less stringent than necessary for this purpose. The provisions do not require 17 that secondary standards be set to eliminate all welfare effects, but rather at a level that protects 18 public welfare from those effects that are judged to be adverse. 19 Staff will prepare at least one draft of the PA document for CASAC review and public 20
comment. The draft PA document will be dist ributed to the CASAC Pb Panel for their 21 consideration and provided to the public for re view and comment. Review by the CASAC Pb 22 Panel will be discussed at public meetings that will be announced in the Federal Register. Based 23 on past practice by CASAC, EPA expects that key advice and r ecommendations for revision of 24 the document would be summarized by the CASAC in a letter to the EPA Administrator. In 25 revising the draft PA document, OAQPS will take into account any such recommendations, and 26 also consider comments received, from CASAC and from the public, at the meeting itself, and 27 any written comments received. The final documen t will be made available on an EPA website, 28 with its public availability a nnounced in the Federal Register. 29

24 The sensitive population groups identified in a NA AQS review may be comprised of low income or minority groups. Where low income/m inority groups are among the sensitiv e groups, the rulemaking decision will be based on providing protection for these and other sensitive population groups. To the extent that low income/minority groups are not among the sensitive groups , a decision based on providing protection of the sensitive groups would be expected to provide protection for the low income/minority groups (as well as any other less sensitive population groups).March 2011 7-3 Draft – Do Not Quote or Cite 

### 7.2 RULEMAKING 1 Following issuance of the final PA and EPA ma nagement consideration of staff analyses 2 and conclusions presented therein, and taki ng into consideration of CASAC advice and 3 recommendations, the Agency will develop a notice of proposed rulemaking. The proposed 4 rulemaking notice conveys the Administrator’s pr oposed conclusions regarding the adequacy of 5 the current standards and any revision that ma y be appropriate. A draft notice of proposed 6 rulemaking will be submitted to the Office of Management and Budget (OMB) for interagency 7 review, in which OMB and other federal agencies are provided the opport unity for review and 8 comment. After the completion of interagency review, EPA will publish the notice of proposed 9 rulemaking in the Federal Register. Monitoring ru le changes associated with review of the Pb 10 standards, and drawing from considerations out lined in chapter 6 above, will be developed and 11 proposed, as appropriate, in conjunc tion with this NAAQS rulemaking. 12 At the time of publication of the notice of proposed rulemaking, all materials on which 13 the proposal is based are made available in the public docket for the rulemaking. 25 Publication 14 of the proposal notice is followed by a public co mment period, generally lasting 60 to 90 days, 15 during which the public is invite d to submit comments on the propos al to the rulemaking docket. 16 Taking into account comments received on the proposed rule, the Agency will then develop a 17 notice of final rulemaking, which again undergoes OMB-coordinated interagency review prior to 18 issuance by EPA of the final rule . In the notice of final rule making, and generally also through 19 the use of an accompanying document, the Agency responds to all significant comments on the 20 proposed rule. 26 Publication of the final rule in the Federal Register completes the rulemaking 21

process. 22

25 The rulemaking docket for the current Pb review is identified as EPA-HQ-OAR-2010-0108. This docket has incorporated the ISA dock et (EPA-HQ-ORD-2011-0051) by reference. Both dockets are publicly accessible at www.regulations.gov

.
26 For example, Agency responses to all substantive comments on the 2008 notice of proposed rulemaking in the last review were provided in th e preamble to the final rule and in a document titled “Response to Responses to Significant Comments on the 2008 Proposed Rule on the National Ambient Air Quality Standards for Lead (May 20, 2008; 73 FR 29184)”, which is available at: http://www.epa.gov/ttn/naaqs/standards/pb/ data/20081015_responsetocomments.pdf.March 2011 8-1 Draft – Do Not Quote or Cite 

## 8 REFERENCES 1

ICF International. (2006) Lead Human Exposure and Health Risk Assessments and Ecological Risk 2 Assessment for Selected Areas. Pilot Phase. Draft Technical Report. Prepared for the U.S. 3 EPA's Office of Air Quality Planning and Standards, Research Triangle Park, NC. 4 December. 5 Jackson, L. (2009) Memorandum from Administrator Li sa Jackson, Subject: Development of 6 regulations and policies. Septem ber 11, 2009. Available at: 7 http://www.epa.gov/ttn/naaqs/pdfs/NAAQSReviewProces sMemo52109.pdf 8 MacDonald, D.D., Ingersoll, C. G., and Berger, T.A. (2000) Developmen t and evaluation of 9 consensus-based sediment qua lity guidelines for freshwate r ecosystems. Archives of 10 Environmental Contamination and Toxicology . 39:20-31. 11 MacDonald, D.D., Ingersoll, C.G. , Smorong, D.E., Lindsk oog, R.A., Sloane, G., and Biernacki, T. 12 (2003) Development and Evaluati on of Numerical Se diment Quality Asse ssment Guidelines 13 for Florida Inland Waters. British Columb ia: MacDonald Environm ental Sciences, Lt. 14 Columbia, MO: U.S. Geological Survey. Prepared for: Florida Department of 15 Environmental Protection, Tallahassee, FL. January. 16

U.S. Environmental Protec tion Agency. (1977) Air qu ality criteria for lead. Research Triangle Park, 17 NC: Health Effects Research Laboratory, Criteria and Specia l Studies Office; EPA report 18 no. EPA-600/8-77-017. Available from: NTIS, Springfield, VA; PB-280411. 19

U.S. Environmental Prot ection Agency. (1986a) Air quality cr iteria for lead. Research Triangle 20 Park, NC: Office of Health and Environmen tal Assessment, Envir onmental Criteria and 21 Assessment Office; EPA report no. EPA-600/ 8-83/028aF-dF. 4v. Available from: NTIS, 22 Springfield, VA; PB87-142378. 23

U.S. Environmental Prot ection Agency. (1986b) L ead effects on cardiovascular function, early 24 development, and stature: an addendum to U.S. EPA Air Qua lity Criteria for Lead (1986). 25 In: Air quality criteria for lead , v. 1. Research Triangle Pa rk, NC: Office of Health and 26 Environmental Assessment, Environmental Cr iteria and Assessment Office; pp. A1-A67; 27 EPA report no. EPA-600/8-83 /028aF. Available from: NT IS, Springfield, VA; PB87- 28 142378. 29

U .S. Environmental Protection Agen cy. (1989) Review of the nationa l ambient air quality standards 30 for lead: Exposure analysis methodology an d validation: OAQPS staff report. Research 31 Triangle Park, NC: Office of Air Quality Pla nning and Standards; report no. EPA-450/2- 32 89/011. Available on the web: 33 http://www.epa.gov/ttn/naaqs/stand ards/pb/data/rnaaqsl_eamv.pdf 34 U.S. Environmental Protection Agen cy. (1990a) Air quality criteria for lead: supplement to the 1986 35 addendum. Research Triangle Park, NC: Office of Health and Envi ronmental Assessment, 36 Environmental Criteria and As sessment Office; report no. EPA/600/8-89/049F. Available 37 from: NTIS, Springfield, VA; PB91-138420. 38March 2011 8-2 Draft – Do Not Quote or Cite U.S. Environmental Protection Agency. (1990b) Review of the national ambient air quality 1 standards for lead: assessment of scientific and technical in formation: OAQPS staff paper. 2 Research Triangle Park, NC: Office of Air Qu ality Planning and Standards; report no. EPA3 450/2-89/022. Available from: NTIS, Springfi eld, VA; PB91-206185. Available on the 4 web: http://www.epa.gov /ttn/naaqs/standards/pb/data/rnaaqsl_asti.pdf 5 U.S. Environmental Protection Agen cy. (1991) U.S. EPA Strategy for Reducing Lead Exposure. 6 Available from U.S. EPA Headquarters Libr ary/Washington, D.C. (Library Code EJBD; 7 Item Call Number: EAP 100/199 1.6; OCLC Number 2346675).. 8

U.S. Environmental Protec tion Agency. (2005) Project Work Plan for Revised Air Quality Criteria 9 for Lead. Research Triangle Park, NC: National Center for Environmental Assessment-RTP 10 Report no. NCEA-R-1465. CASAC Review Draft. 11 U.S. Environmental Protection Agency. (2006a) Plan for Review of the National Ambient Air 12 Quality Standards for Lead. Of fice of Air Quality Planning and Stan dards, Research 13 Triangle Park, NC. Available online at: 14 http://www.epa.gov/ttn/naaqs/sta ndards/pb/s_pb_cr_pd.html 15 U.S. Environmental Protection Agency. (2006b) Air Quality Criteria for Lead. Washington, DC, 16 EPA/600/R-5/144aF. Available online at: www.epa.gov/ncea/ 17

U.S. Environmental Prot ection Agency. (2006c) Analysis Plan for Human Health and Ecological 18 Risk Assessment for the Review of the Lead National Ambi ent Air Quality Standards. 19 Office of Air Quality Planning and Standards, Research Tria ngle Park, NC. Available online 20
at: http://www.epa.gov/ttn/naaqs/standards/pb/s_pb_cr_pd.html 21 U.S. Environmental Protection Agency. (200 7a) Lead: Human Exposur e and Health Risk 22 Assessments for Selected Case Studies, Volume I. Human Exposure and Health Risk 23 Assessments – Full-Scale and Vo lume II. Appendices. Office of Air Quality Planning and 24 Standards, Research Triangle Park, NC. EPA-452/R-07-014a and EPA-452/R-07-014b. 25 U.S. Environmental Protection Ag ency. (2007b) Review of the National Ambient Air Quality 26 Standards for Lead: Policy Assessment of Scientific and Technical Information, OAQPS 27 Staff Paper. EPA-452/ R-07-013. Office of Air Quality Pl anning and Standards, Research 28 Triangle Park, NC. 29 U.S. Environmental Protection Agency. (2010) Integrated Science Assessment for Carbon 30 Monoxide. EPA/600/R-09/019F . National Center for Environmental Assessment-RTP 31 Division, Research Triangle Park, NC. 32March 2011 A-1 Draft – Do Not Quote or Cite 

### Appendix A

Integrated Science Asse ssment for Lead – OutlineMarch 2011 A-2 Draft – Do Not Quote or Cite 

### Integrated Science Assessment for Lead

Chapter 1 Introduction 1.1 Legislative Requirements
1.2 History of Reviews of the NAAQS for Pb 1.3 ISA Development
1.4 Document Organization 1.5 Document Scope 1.6 EPA Framework for Causal Determination 1.7 Summary

Chapter 2 Integrative Overview 2.1 Ambient Pb Sources and Concentrations 2.2 Exposure to Ambient Pb 2.3 Kinetics, Biomarkers, and Models Relating Pb Exposure to Dose Metrics 2.4 Mode of Action 2.5 Pb Health Effects 2.6 Policy Relevant Considerations 2.7 Ecological and Other Welfare Effects 2.8 Integration of Health an d Ecosystem Effects of Pb

Chapter 3 Ambient Pb Source to Concentration 3.1 Introduction 3.2 Sources of Atmospheric Pb 3.3 Fate and Transport of Pb 3.4 Monitoring of Ambient Pb 3.5 Ambient Pb Air Pb Concentrations 3.6 Ambient Pb Concentrations in Non-Air Media and Biota 3.7 Summary

Chapter 4 Toxicokinetics, Biomarkers a nd Models of Pb Burden in Humans 4.1 Pb Exposure Assessment 4.2 Kinetics of Pb 4.3 Biomarkers of Pb 4.4 Empirical Models of Pb Exposure-Blood Pb Relationships 4.5 Biokinetic Models of Pb Exposure-Blood Pb Relationships

Chapter 5 Integrated Health Effects of Pb Exposure 5.1 Introduction 5.2 Modes of Action 5.3 Neurotoxic Effects of Pb 5.4 Cardiovascular Effects of Pb 5.4.1 Mortality Effects 5.5 Renal Effects 5.6 Effects of Pb on the Immune System 5.7 Carcinogenic and Genotoxic Potential of PbMarch 2011 A-3 Draft – Do Not Quote or Cite 5.8 Effects of Pb on Heme Synthesis and RBC Function 5.9 Effects of Pb on the Reproductive System 5.10 Effects of Pb on Other Organ Systems 5.11 Summary

Chapter 6 Susceptible Populations 6.1 Susceptibility Factors and Biomarkers of Pb Exposure 6.2 Susceptibility Factors Relate d to Pb-induced Health Effects 6.3 Summary

Chapter 7 Ecological Effects a nd Other Welfare Effects of Pb 7.1 Introduction to Ecological Concepts 7.2 Terrestrial Ecosystem Effects 7.3 Aquatic Ecosystem Effects 7.4 SummaryUnited StatesEnvironmental ProtectionAgencyOffice of Air Quality Planning and StandardsHealth and Environmental Impacts DivisionResearch Triangle Park, NCPublication No. EPA-452/D-11-001March 2011